Novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors

ABSTRACT

The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and/or long term regulation of energy balance; short-, medium- and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, adiposity and/or obesity; body weight gain and/or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy).

REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. provisional application60/707,941 filed Aug. 15, 2005, U.S. provisional application 60/787,543filed Mar. 31, 2006, and European application 05017732.8 filed Aug. 16,2005, all of which are incorporated herein by reference.

TECHNICAL FIELD

The invention relates to novel triazole derivatives that act as ghrelinanalogue ligands of growth hormone secretagogue receptors. Thesecompounds are useful in modulating growth hormone plasma levels inmammals as well as in the treatment and/or regulation of variousphysiological and pathophysiological conditions, such as growthretardation, obesity, food intake, energy balance, tumor cellproliferation, wound/burn healing, metabolic disorders and inflammation.

BACKGROUND OF THE INVENTION

Ghrelin, a 28 amino acid peptide with a unique octanoyl modification onSer-3 (Kojima M et al., Nature 1999, 402: 656-660), was identified as anendogenous ligand for the growth hormone secretagogue receptor type 1a(GHS-R 1a), a G-protein coupled receptor (Howard A D et al., Science1996, 273: 974-977). Ghrelin is essentially produced in the upperintestinal tract/stomach but lower amounts were also detected in bowel,pancreas, kidney, the immune system, placenta, testes, pituitary, lungand in the hypothalamus (van der Lely A J et al., Endocrine Rev. 2004,25: 426-457; Cowley M et al., Neuron 2003, 37: 649-661).

In humans, ghrelin stimulates growth hormone (GH) via a pathwayindependent from GHRH receptor and in synergy with GHRH on GH secretion(Arvat E et al., J. Clin. Endocrinol. Metab. 2001, 86: 1169-1174).Besides, it also stimulates ACTH, prolactin, cortisol, aldosterone andepinephrine secretion (Arvat E et al., J. Clin. Endocrinol. Metab. 2001,86: 1169-1174; Nagaya N et al., Am. J. Physiol. Regul. Integr. Comp.Physiol. 2001, 280: R1483-1487; Takaya K et al., J. Clin. Endocrinol.Metab. 2000, 85: 4908-4911).

Ghrelin is thought to participate in metabolism regulation and energyexpenditure, so ghrelin expression and secretion into the generalcirculation from the stomach is expected to be influenced by metabolichormones. In obese humans, plasma ghrelin levels are reduced, suggestingthat the elevated insulin or leptin levels of obese subjects lowerghrelin secretion (Tschop M et al, Diabetes 2001, 50: 707-709).

The release of growth hormone in humans and animals is believed to treatphysiological or pathophysiological conditions characterized by adeficiency in growth hormone secretion as well as to treat thoseconditions which are improved by the anabolic effects of growth hormone.

Initially, clinical applications with GH were limited to treatment ofGH-deficient children, but the commercialization of recombinant humangrowth hormone (rhGH) allowed many studies which showed other potentialclinical uses of GH (Strobl J S et al., Pharmacol. Rev. 1994, 46: 1-34;Torosian M H, J. Pediatr. Endocrinol. 1993, 6: 93-97). rhGH has shownpromise in the treatment of patients with burns, wounds, bone fracturesand more recently in reversing the catabolic effects of glucocorticoids,chemotherapy and AIDS as well as in modifying body composition (Rudman Det al., N. Engl. J. Med. 1990, 323: 1-6; Papadakis M A et al., Ann.Intern. Med. 1996, 124: 708-716; Welle S et al., J. Clin. Endocrinol.Metab. 1996, 81: 3239-3243).

GH, synthesized and stored in the pituitary gland, is released under thecontrol of two known hypothalamic hormones: growth hormone releasinghormone (GHRH) and the inhibitory hormone somatostatin (SRIF). In mostcases, GH deficiency is related to a hypothalamic defect and not to apituitary deficiency in GH. Therefore, as an alternative treatment torhGH, GH-deficient patients could also be treated with any compound thatreleases endogenous GH from the pituitary gland. This can either beperformed with GHRH which stimulates GH release but also with syntheticgrowth hormone secretagogues (GHS).

Many synthetic, peptidyl and non-peptidyl GHS, such as GHRPs 1, 2 and 6,Hexarelin, MK-0677, EP-01572, were shown to specifically bind to thethen orphan receptor GHS receptor—several of them long before ghrelinand ghrelin/GHS receptor were discovered (see Camanni F et al., FrontNeuroendocrinol. 1998, 19: 47-72; Casanueva F F et al., TrendsEndocrinol. Metab. 1999, 10: 30-38; van der Lely A J et al., EndocrineRev. 2004, 25: 426-457 for further references). GHS also show potent GHreleasing action and have the same biological activities as mentionedabove for ghrelin.

GHS were also disclosed in the following patents or patent applications(not exhaustive list): U.S. Pat. No. 6,071,926, U.S. Pat. No. 6,329,342,U.S. Pat. No. 6,194,578, US 2001/0041673, U.S. Pat. No. 6,251,902, US2001/0020012, US 2002/0013320, US 2002/0002137, WO 95/14666, WO96/15148, WO 01/96300.

While the ghrelin/GHS induced GH secretion is mediated by the activationof the ghrelin/GHS receptor type 1a (GHS-R 1a), there is evidence so farthat at least some of the other effects of ghrelin and GHS are alsomediated by different receptors of the GHS receptor family or evendifferent binding sites on a given GHS receptor.

GHS receptors are concentrated in the hypothalamus-pituitary area butappear also to be distributed in other central and peripheral tissues(Hattori N et al., J. Clin. Endocrinol, Metab. 2001, 86: 4284-4291;Gnanapavan S et al., J. Clin, Endocrinol. Metab. 2002, 87: 2988-2991;Muccioli G et al., J. Endocrinol. 2000, 157: 99-106; Muccioli G et al.,Ann. Endocrinol. 2000, 61: 27-31; Muccioli G et al., Eur. J. Pharmacol.2002, 440: 235-254; Papotti M et al., J. Clin. Endocrinol. Metab. 2000,85: 3803-3807; Cassoni P et al., J. Clin. Endocrinol, Metab. 2001, 86:1738-1745; Guan X M et al., Brain Res. Mol. Brain Res. 1997, 48: 23-29;Bluet-Pajot M T et al., Endocrine 2001, 14: 1-8; Korbonits M et al., J.Clin, Endocrinol. Metab, 1998, 83: 3624-3630).

Two GHS type 1 receptors have been identified, GHS-R 1a and GHS-R 1b,that in human are presumably expressed by a single gene andalternatively spliced (van der Lely A J et al., Endocrine Rev. 2004, 25:426-457; Howard A D et al., Science 1996, 273: 974-977; Smith R G etal., Endocr. Rev. 1997, 18: 621-645; Smith R G et al., Endocrine 2001,14: 9-14; McKee K K et al., Mol. Endocrinol. 1997, 11: 415-423;Petersenn S, Minerva Endocrinol. 2002; 27: 243-256). Among mammalianspecies a high degree of sequence identity has been reported for GHS-R1a (Petersenn S, Minerva Endocrinol. 2002; 27: 243-256: between 91.8%and 95.6%).

Motilin receptor, was discovered as a member of the GHS receptor family,having 52% identity (Smith R G et al., Endocrine 2001, 14: 9-14; McKee KK et al., Genomics 1997, 46: 426-434). Gastrointestinal motilin receptor1a and GHS-R 1a show a high similarity (Smith R G et al., Endocrine2001, 14: 9-14; Feighner S D et al., Science 1999, 284: 2184-2188).

Other GHS receptor family members appear to be neurotensin receptor, TRHreceptor, GPR38 (FM1), GPR39 (FM2) and FM3 (Smith R G et al., Endocr.Rev. 1997, 18: 621-645; Smith R G et al., Horm. Res. 1999, 51 (Suppl.3): 1-8; Tan C P et al., Genomics 1998, 52: 223-229; Howard A D et al.,Science 1996, 273: 974-977). Further GHS receptor subtypes appear toexist in a wide variety of central and peripheral tissues (van der LelyA J et al., Endocrine Rev. 2004, 25: 426-457). For instance, a cardiacGHS-R has been reported (Bodart V et al., Circ. Res. 1999, 85: 796-802)with a predicted sequence similar to that of CD36, a multifunctionalreceptor known as glycoprotein IV (Bodart V et al., Circ. Res. 2002, 90:844-849). Cassoni et al. (J. Clin. Endocrinol. Metab. 2001, 86:1738-1745) report the existence of GHS-R subtypes in neoplastic mammarycells that are activated by ligands binding to specific binding sitesdifferent from the classical GHS-R type 1. Furthermore, data gathered bythese authors support the hypothesis that even different binding sitesubtypes do exist for GHS-R in peripheral organs, which are possibly dueto their endocrine or non-endocrine, but also on their normal orneoplastic nature.

The ubiquity of GHS binding sites explains that independently from theirstrong growth hormone secretagogue properties, ghrelin as well assynthetic GHS are implicated in several important physiological andpathophysiological conditions.

Accordingly, potential clinical applications include among others

-   -   a) Short-, medium- and long term regulation of energy balance        and/or food intake (Tschop M et al., Nature 2000, 407: 908-913;        Asakawa A et al., Gut 2003, 52: 947-952; US 2001/0020012; Kojima        M et al., Curr. Opin. Pharmacol. 2002, 2: 665-668; Horvath T L        et al., Curr. Pharm. Des. 2003, 9: 1383-1395; Wren A M et        al., J. Clin. Endocrinol. Metab. 2001, 86: 5992-5995)    -    Expression of GHS-R1a has been shown on neurons of hypothalamus        paraventricular nucleus. These neurons send efferents onto key        hypothalamic circuits for the control of food intake, like the        arcuate nucleus which produces the mediator NPY. It is thought        that the stimulation of food intake by ghrelin and/or GHS is        mediated by an increase of NPY in the arcuate nucleus (Willesen        M G et al., Neuroendocrin. 1999, 70: 306-316). Single        administration (icv or ip) of anti-ghrelin IgG suppressed acute        feeding in lean rats (Bagnasco M et al., Regul. Pept. 2003, 111:        161-167). Chronic twice-daily icv administration of anti-ghrelin        IgG reduced body weight over a five-day period (Murakami N et        al., J. Endocrinol. 2002, 174: 283-288).    -    A recent study using a peptidic GHS-R 1a antagonist,        [D-Lys-3]-GHRP-6, showed a reduction of food intake and body        weight gain in diet induced obese mice (Asakawa A et al., Gut,        2003, 52: 947-952). The fact that peptidyl compounds, initially        characterized as growth hormone secretagogues, are able to        stimulate selectively food intake in rats without inducing        growth hormone secretion, suggests the existence of a GHS-R        subtype different from GHS-R 1a in the hypothalamus (Torsello A        et al., Neuroendocrin. 2000, 72: 327-332; Torsello A et al.,        Eur. J. Pharmacol. 1998, 360: 123-129).    -   b) Treatment of adipogenesis, adiposity and/or obesity and        reduction of body weight (Tschop M et al., Nature 2000, 407:        908-913; Asakawa A et al., Gut 2003, 52: 947-952)    -    Chronic administration of ghrelin and/or GHS in freely feeding        mice and rats results in increased body weight and decreased fat        utilization (Tschop M et al., Nature 2000, 407: 908-913).        Furthermore, it has been reported that ghrelin and des-octanoyl        ghrelin promote adipogenesis in vivo (Thompson N M et al.,        Endocrinol. 2004, 145: 234-242) and inhibit        isoproterenol-induced lipolysis in rat adipocytes via a non-type        GHS-R 1a (Muccioli G et al., Eur. J. Pharmacol. 2004, 498:        27-35). On the other hand, there is also a report describing        that the expression of the GHS-R1a in rat adipocytes increases        with age and during adipogenesis (Choi K et al., Endocrinol.        2003, 144, 754-759).    -   c) Treatment of tumor cell proliferation    -    As in the case for other members of the hypothalamus-pituitary        axis which regulates the secretion of growth hormone, evidence        is emerging to indicate that ghrelin and GHS-receptors may play        an important autocrine/paracrine role in some cancers (Jeffery P        L et al., Cytokine Growth Factor Rev. 2003, 14: 113-122).        Specific binding sites for ghrelin, peptidyl- and non-peptidyl        GHS are present in tumoral tissues, like prostate cancer cell        line PC3 (Jeffery P L et al., J. Endocrinology 2002, 172:        R7-R11), thyroid tissue (Cassoni P et al., J. Endocrinol. 2000,        165: 139-146), lung carcinoma cells CALU-1 (Ghè C et al.,        Endocrinol. 2002, 143: 484-491) and breast carcinomas (Cassoni P        et al., J. Clin. Endocrinol. Metab. 2001, 86: 1738-1745).    -    In the case of breast, the specific binding sites for GHS were        found in tumoral tissue while the normal mammary parenchyma did        not reveal such receptors. Synthetic GHS have been reported to        inhibit the proliferation of lung carcinoma cells CALU-1 (Ghè C        et al., Endocrinol. 2002, 143: 484-491) and that of breast        carcinoma cell lines (Cassoni P et al., J. Clin. Endocrinol.        Metab. 2001, 86: 1738-1745).    -    Both ghrelin and non-acylated ghrelin bind to tumoral tissues.        Because non-acylated ghrelin is unable to bind the GHS-R1a, it        is likely that the binding site of GHS to tumoral tissues is        different from the GHS-R1a. From these data, one can anticipate        that the binding site in tumoral tissues recognizes ligands of        the GHS-R1a and in addition other not yet characterized chemical        structures. Synthetic ligands of GHS-R1a may have therefore the        potential to inhibit the proliferation of tumor cells expressing        subtypes of GHS receptors.    -   d) Treatment of inflammation/anti-inflammatory effects    -    The anti-inflammatory effect of the ghrelin agonist growth        hormone-releasing peptide-2 (GHRP-2) in chronic arthritis with        clinical manifestations of hypermetabolism and cachexia was        demonstrated (Granado M et al., Am. J. Physiol. Endocrinol.        Metab. 2005, 288: E486-492). These data suggest that the        anti-inflammatory action of GHRP-2 is mediated by activation of        ghrelin receptors expressed by immune competent cells.    -   e) Treatment of cachexia    -    The anti-cachetic effect of administered recombinant growth        hormone in an animal model of chachexia (Roubenoff R et al.,        Arthritis Rheum. 1997, 40(3): 534-539) could be demonstrated        (Ibanez de Caceres I et al., J. Endocrin. 2000, 165(3):        537-544). The findings are also in line with data of patients        with rheumatoid arthritis (Roubenoff R et al., J Clin Invest.        1994, 93(6): 2379-2386).    -   f) Treatment of gastrectomy (ghrelin replacement therapy)    -    The gastric hormone ghrelin was given to mice subjected to        gastrectomy or sham operation (Dornonville de la Cour C et al.,        Gut 2005, 54(7): 907-913). The results presented show that        ghrelin replacement therapy at least partially reverse        gastrectomy induced reduction in body weight and body fat.    -   g) Treatment of (gastric) postoperative ileus    -    The effect of ghrelin on the motor function of the        gastrointestinal tract in rat was evaluated. It could be shown        that ghrelin reverses the delayed gastric evacuation and is a        strong prokinetic agent useful for the treatment/reversion of        postoperative gastric ileus (Trudel L et al., Am J Physiol        Gastrointest Liver Physiol 2002, 282(6): G948-G952).    -   h) Treatment of diabetes (diabetes type I and type II)    -    The effect of ablation of ghrelin in leptin-deficient mice was        studied (Sun et al., Cell Metabolism 2006, 3: 379-386). The        results show that deletion of ghrelin augments insulin secretion        in response to glucose challenge indicating that inhibition of        ghrelin or counteracting its activity may be a possible way for        the treatment of diabetes including its subtypes I and II (see        also WO 03/051389).

Further fields of application comprise acceleration of recovery ofpatients having undergone major surgery (e.g. U.S. Pat. No. 6,194,578);accelerating the recovery of burn patients (e.g. U.S. Pat. No.6,194,578); attenuating protein catabolic response after a majoroperation (e.g. U.S. Pat. No. 6,194,578); reducing cachexia and proteinloss due to acute or chronic illness (e.g. U.S. Pat. No. 6,194,578);treating central nervous system disorders of patients undergoing amedical procedure in combination with antidepressants (e.g. US2002/0002137 A1); acceleration of bone fracture repair and cartilagegrowth (e.g. U.S. Pat. No. 6,194,578); treatment or prevention ofosteoporosis; stimulation of the immune system; accelerating woundhealing (e.g. U.S. Pat. No. 6,194,578); treatment of growth retardationassociated with the Prader-Willi syndrome, Turner's syndrome andobesity; treatment of intrauterine growth retardation, skeletaldysplasia, hypercortisolism and Cushing's syndrome; treatment ofosteochondrodysplasias, Noonan's syndrome, schizophrenia, depressionsand Alzheimer's disease; treatment of pulmonary dysfunction andventilator dependency; treatment of hyperinsulinemia includingnesidioblastosis; adjuvant treatment for ovulation induction; preventionof the age-related decline of thymic function; improvement in musclestrength and mobility (e.g. U.S. Pat. No. 6,194,578); maintenance ofskin thickness (e.g. U.S. Pat. No. 6,194,578); improvement of sleepquality (e.g. U.S. Pat. No. 6,071,926); prevention of congestive heartfailure alone (e.g. U.S. Pat. No. 6,329,342; U.S. Pat. No. 6,194,578)and in combination with corticotropin releasing factor antagonists (e.g.US 2001/0041673); metabolic homeostasis or renal homeostasis (e.g. inthe frail elderly)(e.g. U.S. Pat. No. 6,194,578); improving glycemiccontrol (e.g. U.S. Pat. No. 6,251,902); treatment of systemic lupuserythematosus and inflammatory bowel disease (e.g. US 2002/0013320);treating or preventing frailty associated with aging or obesity (e.g.U.S. Pat. No. 6,194,578); as well as stimulation of osteoblasts.

Animals were not forgotten in potential applications such as stimulationof food intake (Wren A M et al., Diabetes 2001, 50: 2540-2547),stimulation of the immune system in companion animals and treatment ofdisorder of aging, growth promotion in livestock and stimulation of woolgrowth in sheep.

Compounds containing triazole moieties have been widely recognized inthe medicinal chemistry due to their various biological activities. Thefollowing patent families are all directed to heterocyclic compoundsthat are said to show certain biological action for use in differentmedicinal indications. Triazole moieties are implicitly or explicitlycontained. However, neither of these patent families mentions ghrelinanalogue ligands of the GHS receptor family nor modulation of thesereceptors nor GH secretagogue properties or the like.

WO 2004/111015 discloses modulators of the glucocorticoid receptor. WO2004/052280 describes anti-agiogenic compounds as inhibitors of tyrosinekinase activity of VEGF receptors and their use in cancer. WO2004/096795 also discloses tyrosine kinase inhibitors, preferably C-FMSinhibitors, WO 03/011831 and WO 03/011210 both describeheteroarylheteroalkylamine derivatives as inhibitors of nitric oxidesynthase. WO 02/00651 is directed to Factor XA inhibitors for use inthromboembolic disorders. WO 01/94318 and WO 01/94317 both describechemical libraries of substituted azole derivatives and methods of theirsynthesis for use in drug discovery high-throughput screening. However,they fail to provide any biological activity or any medicinal use nor dothey name specific compounds. WO 00/76971 and WO 00/76970 both claimserine protease inhibitors useful as antithrombotic agents. WO 01/36395discloses triazole derivatives as farnesyl transferase inhibitors. WO96/33176 and U.S. Pat. No. 5,703,092 are directed to hydroxamic acidcompounds as metalloprotease and TNF inhibitors. WO 93/09095 describes2-heterocyclicethylamine derivatives and their use in neurological andneurodegenerative disorders. WO 2004/103270 claims compounds for thetreatment of thrombosis, in particular Factor XIa inhibitors. WO98/38177, U.S. Pat. No. 6,506,782, U.S. Pat. No. 6,849,650 and US2003/0130188 all describe heterocyclic compounds as inhibitors ofbeta-amyloid peptide release or its synthesis for use in Alzheimer'sdisease.

Heterocyclic compounds that may be useful as GHS have also beendescribed in the literature.

WO 00/54729, for instance, discloses heterocyclic aromatic compounds asGH secretagogues which are said to stimulate endogenous productionand/or release of GH and can also contain triazole moieties. Inaddition, a method for increasing levels of endogenous GH or increasingthe endogenous production or release of GH administering such GHS isdescribed. Furthermore, a method is provided for preventing or treatingosteoporosis (improving bone density and/or strength), or treatingobesity, or increasing muscle mass and/or muscle strength and functionin elderly humans, or reversal or prevention of frailty in elderlyhumans administering such GHS.

However, although claiming in vivo GH release WO 00/54729 fails toactually prove such effect. Neither in vitro nor in vivo data arecontained that demonstrate any stimulation of or increase in endogenousproduction and/or release of GH.

Besides, WO 00/54729 fails to describe and show action of those claimedcompounds on any biological target, i.e. claimed compounds are notshown/described to be ligands of one or more specific receptors, forinstance of a receptor family, that bind to them and modulate theiractivity.

Furthermore, WO 00/54729 fails to describe and demonstrate inhibitoryand/or antagonistic activity of claimed compounds. As a matter of fact,such compounds are not shown to decrease levels of endogenous GH and/orinhibit or decrease endogenous production and/or release of GH. Nor isan inhibitory action on any receptor mentioned nor made obvious.

U.S. Pat. No. 6,525,203, U.S. Pat. No. 6,518,292 U.S. Pat. No. 6,660,760are members of the same patent family as WO 00/54729 that, however, donot comprise triazole moieties as claimed subject matter any more. Withregard to biological activity, the above stated facts as for WO 00/54729apply.

WO 2004/021984 describes heterocyclic aromatic compounds GHsecretagogues which are said to be useful in stimulating endogenousproduction or release of GH. However, claimed compounds consists of bi-to tetracylic aromatic rings and do not contain triazoles.

Analogous to WO 00/54729 in vivo GH release is claimed, but neither invitro nor in vivo data are contained that demonstrate any stimulation ofor increase in endogenous production and/or release of GH. With regardto biological activity, the same stated facts as for WO 00/54729 apply.

WO 97/23508 claims compounds of peptide mimetic nature as GHS and aresaid to act directly on pituitary cells in vitro to release GH therefromand show improved properties, such as improved resistance to proteolyticdegradation and improved bioavailability. In addition, claimed compoundscould also be administered in vivo to increase GH release. The compoundsare peptide derivatives and do not explicitly contain triazole moieties.

However, once again and in analogy to above WO 00/54729 and WO2004/021984, WO 97/23508 fails to exhibit any in vitro or in vivo datathat demonstrate the claimed effects such as direct action on pituitarycells, GH release therefrom and improved properties. Furthermore, withregard to biological targets and inhibitory/antagonistic activity, theabove stated facts as for WO 00/54729 apply.

U.S. Pat. No. 6,127,391, U.S. Pat. No. 5,977,178 and U.S. Pat. No.6,555,570 are members of the same patent family as WO 97/23508. Thefacts as stated for WO 97/23508 do apply.

BRIEF DESCRIPTION OF THE Invention

The present invention has as one object to provide novel compounds whichcan be employed for the treatment of physiological and/orpathophysiological conditions in mammals, in particular humans, that aremediated by GHS receptors. It is another object of the underlyinginvention to provide compounds for the above treatment where thetreatment is achieved by modulation of GHS receptors. A further objectof the present invention is to provide antagonists of GHS receptors forthose treatments. It is yet another object of the underlying inventionto provide agonists of GHS receptors for those treatments.

The object of the invention has been surprisingly solved in one aspectby providing compounds according to formula (I)

wherein:

-   -   R1 and R2 are independently of one another selected from the        group consisting of hydrogen atom, alkyl, alkenyl, alkynyl,        cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,        heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl,        arylsulfonyl, arylalkylsulfonyl which are optionally substituted        in the alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl,        arylalkyl, heteroarylalkyl, heterocyclyl and/or        heterocyclylalkyl group by up to 3 substituents independently        selected from the group consisting of halogen, —F, —Cl, —Br, —I,        —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl, aryl, arylalkyl, —O-alkyl,        —O-aryl, —O-arylalkyl; and preferably are selected from the        group consisting of alkyl, aryl, heteroaryl, arylalkyl,        heteroarylalkyl optionally being substituted by up to 3        substituents independently selected from the group consisting of        halogen, —F, —Cl, —Br, —I, —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl,        aryl, arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl;    -   one of radicals R3 and R4 is a hydrogen atom, whereas the other        radical is selected from the group consisting of hydrogen atom,        alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl,        heterocyclyl, heterocyclylalkyl, -alkyl-O-aryl,        -alkyl-O-arylalkyl, -alkyl-O-heteroaryl,        -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl,        alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl,        -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl,        -alkyl-CO-heterocyclyl, -alkyl-CO-heterocyclylalkyl,        -alkyl-C(O)O-aryl, -alkyl-C(O)O-arylalkyl,        -alkyl-C(O)O-heteroaryl, -alkyl-C(O)O-heteroarylalkyl,        -alkyl-C(O)O-heterocyclyl, -alkyl-C(O)O-heterocyclylalkyl,        -alkyl-CO—NH₂, -alkyl-CO—OH, -alkyl-NH₂, -alkyl-NH—C(NH)—NH₂,        alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, alkyl-5-alkyl,        alkyl-S—H which are optionally substituted in the aryl,        heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/or        heterocyclylalkyl group by up to 3 substituents independently        selected from the group consisting of halogen, —F, —Cl, —Br, —I,        —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl, aryl, arylalkyl, —O-alkyl,        —O-aryl, —O-arylalkyl; and preferably are selected from the        group consisting of arylalkyl, heteroarylalkyl,        heterocyclylalkyl, -alkyl-O-aryl, -alkyl-O-arylalkyl,        -alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl,        -alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl,        -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl,        -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl,        alkyl-CO-heterocyclylalkyl, -alkyl-C(O)O-aryl,        -alkyl-C(O)O-arylalkyl, -alkyl-C(O)O-heteroaryl,        -alkyl-C(O)O-heteroarylalkyl, -alkyl-C(O)O-heterocyclyl,        -alkyl-C(O)O-heterocyclylalkyl, -alkyl-CO—NH₂, -alkyl-CO—OH,        -alkyl-NH₂, -alkyl-NH—C(NH)—NH₂, optionally being substituted in        the aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl        and/or heterocyclylalkyl group by up to 3 substituents        independently selected from the group consisting of halogen, —F,        —Cl, —Br, —I, —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl, aryl,        arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl;    -   R5 is selected from the group consisting of hydrogen atom,        alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,        heteroarylalkyl, heterocyclyl, heterocyclylalkyl, —CO-alkyl,        —CO-cycloalkyl, —CO-cycloalkylalkyl, —CO-aryl, —CO-arylalkyl,        —CO-heteroaryl, —CO-heteroarylalkyl, —CO-heterocyclyl,        —CO-heterocyclylalkyl, —CO—C*(R9R10)-NH₂, —CO—CH₂—C*(R9R10)-NH₂,        —CO—C*(R9R10)-CH₂—NH₂, alkylsulfonyl, arylsulfonyl,        arylalkylsulfonyl which are optionally substituted by up to 3        substituents independently selected from the group consisting of        halogen, —F, —Cl, —Br, —I, —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl,        aryl, arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl; and preferably        is selected from the group consisting of hydrogen atom,        —CO-alkyl, —CO-cycloalkyl, —CO-aryl, —CO-heteroaryl,        —CO-arylalkyl, —CO-heteroarylalkyl, —CO-heterocyclyl,        —CO—C*(R9R10)-NH₂, —CO—CH₂—C*(R9R10)-NH₂, —CO—C*(R9R10)-CH₂—NH₂,        optionally being substituted by up to 3 substituents        independently selected from the group consisting of halogen, —F,        —Cl, —Br, —I, —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl, aryl,        arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl;    -   R6 is selected from the group consisting of hydrogen atom,        alkyl, cycloalkyl, cycloalkylalkyl and preferably is a hydrogen        atom;    -   R7 and R8 are independently of one another selected from the        group consisting of hydrogen atom, alkyl, cycloalkyl,        cycloalkylalkyl and preferably are a hydrogen atom;    -   R9 and R10 are independently of one another selected from the        group consisting of hydrogen atom, alkyl natural alpha-amino        acid side chain, unnatural alpha-amino acid side chain and        preferably are selected from the group consisting of hydrogen        atom, alkyl;    -   m is 0, 1 or 2 and preferably is 0; and    -   * means a carbon atom of R or S configuration when chiral;

that can be used for the manufacture of a medicament for the treatmentor prophylaxis of physiological and/or pathophysiological conditions inmammals that are mediated by GHS receptors.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-13 show the measured competition plots of the GHS-R 1areceptor-ligand binding assay with ¹²⁵I-His⁹-ghrelin and selectedcompounds 9, 31, 39, 45, 50, 62, 64, 71, 73, 74, 79, 81 and 90 asdescribed in II) of the example section.

FIGS. 14-40 show the calculated dose-response plots of the in vitrointracellular Calcium release assay with human GHS-R 1a transfected CHOcells of the selected compounds 1, 9, 12, 20, 22, 31, 39, 41, 42, 45,46, 47, 48, 49, 50, 51, 55, 62, 64, 67, 71, 73, 74, 79, 81, 90 andghrelin as described in III) of the example section as well as EC₅₀ andKI values for GHS receptor agonists and IC₅₀ and Kb values for GHSreceptor antagonists.

FIGS. 41-46 show the effects of selected compounds 9, 38, 50, 64, 74, 81on the isoprorerenol-induced lipolysis inhibition curve of unacylatedghrelin (UAG) in primary adipocytes from mice under diet-induced obesityas described in VIII) of the example section.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In a preferred embodiment compounds according to above formula (I) areprovided, where

-   -   R3 is selected from the group consisting of -alkyl-CO-aryl,        -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl,        -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl,        alkyl-CO-heterocyclylalkyl, -alkyl-C(O)O-aryl,        -alkyl-C(O)O-arylalkyl, -alkyl-C(O)O-heteroaryl,        -alkyl-C(O)O-heteroarylalkyl, -alkyl-C(O)O-heterocyclyl,        -alkyl-C(O)O-heterocyclylalkyl, -alkyl-CO—NH₂, -alkyl-CO—OH,        -alkyl-NH—C(NH)—NH₂, alkyl-5-alkyl, alkyl-S—H, and preferably is        selected from the group consisting of -alkyl-CO-arylalkyl,        -alkyl-C(O)O-arylalkyl, -alkyl-CO—NH₂, -alkyl-CO—OH;

that can be used for the manufacture of a medicament for the treatmentor prophylaxis of physiological and/or pathophysiological conditions inmammals that are mediated by GHS receptors.

In another preferred embodiment compounds according to above formula (I)are provided, where

-   -   R4 is a hydrogen atom;    -   R5 is selected from the group consisting of hydrogen atom,        alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,        heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl,        arylsulfonyl, arylalkylsulfonyl, —CO-cycloalkyl,        —CO-cycloalkylalkyl, —CO-aryl, —CO-arylalkyl, —CO-heteroaryl,        —CO-heteroarylalkyl, —CO-heterocyclyl, —CO-heterocyclylalkyl;    -   with the proviso that if R5 is —CO-heteroarylalkyl, heteroaryl        is not imidazole; and    -   with the proviso that if R5 is —CO-heterocyclyl and heterocyclyl        contains only nitrogen atoms as heteroatoms, that at least two        nitrogen atoms are contained in heterocyclyl; and    -   with the proviso that if R5 is —CO-heterocyclylalkyl and        heterocyclyl contains only nitrogen atoms as heteroatoms that in        the case that one or two nitrogen atoms are contained in        heterocyclyl no nitrogen atom is positioned at position 1 of        heterocyclyl that is the atom directly linking heterocyclyl to        the carbonyl group —CO—;    -   where alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl,        arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl,        alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, —CO-cycloalkyl,        —CO-cycloalkylalkyl, —CO-aryl, —CO-arylalkyl, —CO-heteroaryl,        —CO-heteroarylalkyl, —CO-heterocyclyl, and/or        —CO-heterocyclylalkyl are optionally substituted by up to 3        substituents independently selected from the group consisting of        halogen, —F, —Cl, —Br, —I, —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl,        aryl, arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl;    -   with the proviso that if R5 is —CO-cycloalkyl or        —CO-cycloalkylalkyl, R5 is not substituted with NR7R8 at        position 1 of cycloalkyl, that is the C atom directly linking        cycloalkyl to the carbonyl group —CO— in case of        R5=—CO-cycloalkyl or to the alkyl in case        R5=—CO-cycloalkylalkyl; and    -   with the proviso that if R5 is —CO-aryl or —CO-arylalkyl and        aryl is phenyl/benzene and is only substituted with one        substituent, this one substituent is not —NR7R8;    -   R6 is a hydrogen atom;    -   R7 and R8 are independently of one another selected from the        group consisting of hydrogen atom, alkyl, cycloalkyl,        cycloalkylalkyl and preferably are a hydrogen atom; and    -   m is 0, 1 or 2, and more preferably is 0;

that can be used for the manufacture of a medicament for the treatmentor prophylaxis of physiological and/or pathophysiological conditions inmammals that are mediated by GHS receptors.

In a further aspect, the object of the invention has surprisingly beenachieved by providing compounds according to formula (I), where

-   -   R1 is selected from the group consisting of hydrogen, methyl,        (2-methoxyphenyl)-methyl, (3-methoxyphenyl)-methyl,        (4-methoxyphenyl)-methyl, (3-methoxyphenyl)-ethyl,        (4-methoxyphenyl)-ethyl, phenyl, phenyl-methyl, phenyl-ethyl,        (4-ethylphenyl)-methyl, (4-methylphenyl)-methyl,        (4-fluorophenyl)-methyl, (4-bromophenyl)-methyl,        (2,4-dimethoxyphenyl)-methyl, (3,5-dimethoxyphenyl)-methyl,        2,2-diphenyl-ethyl, naphthaline-1-yl-methyl,        1H-indole-3-yl-methyl, 2-(1H-indole-3-yl)-ethyl,        3-(1H-indole-3-yl)-propyl, 4-methyl-phenyl, 4-ethyl-phenyl,        n-hexyl, (3,4-dichlorophenyl)-methyl, (4-nitro-phenyl)-methyl,        (pyridine-2-yl)-methyl, (pyridine-3-yl)-methyl,        (pyridine-4-yl)-methyl, (thiophene-2-yl)-methyl,        (thiophene-3-yl)-methyl, (furan-2-yl)-methyl,        (furan-3-yl)-methyl;    -   R2 is selected from the group consisting of methyl,        1H-indole-3-yl-methyl, 2-(1H-indole-3-yl)-ethyl,        3-(1H-indole-3-yl)-propyl, 2-phenyl-ethyl, 3-phenyl-propyl,        4-phenyl-butyl, 2-methoxy-phenylmethyl, 3-methoxy-phenylmethyl,        4-methoxy-phenylmethyl, 2-methoxy-phenylethyl,        3-methoxy-phenylethyl, 4-methoxy-phenylethyl;    -   R3 is selected from the group consisting of hydrogen atom,        methyl, propan-2-yl, 2-methyl-propan-1-yl, butan-2-yl,        butan-1-yl, —CH₂—SH, —(CH₂)₂—S—CH₃, 1H-indole-3-yl-methyl,        phenyl-methyl, 2-phenyl-ethyl, —CH₂—O—CH₂-phenyl,        —CH₂—CO—CH₂-phenyl, —(CH₂)₂—CO—CH₂-phenyl, —CH₂—C(O)O-phenyl,        —(CH₂)₂—C(O)O-phenyl, hydroxy-methyl, 1-hydroxy-ethan-1-yl,        —CH₂—CO—NH₂, —(CH₂)₂—CO—NH₂, (1-hydroxy-benzene-4-yl)-methyl,        —CH₂—CO—OH, —(CH₂)₂—CO—OH, —(CH₂)₄—NH₂,        (1H-imidazol-5-yl)-methyl, —(CH₂)₃—NH—C(NH)—NH₂, —(CH₂)₃—NH₂,        —(CH₂)₃—NH—CO—NH₂, and preferably is selected from the group        consisting of 1H-indole-3-yl-methyl, —CH₂—CO—CH₂-phenyl,        —(CH₂)₂—CO—CH₂-phenyl, —CH₂—C(O)O-phenyl, —(CH₂)₂—C(O)O-phenyl;    -   R4 is a hydrogen atom;    -   R5 is selected from the group consisting of hydrogen atom,        —CO—CH₂—NH₂ (Gly residue), —CO—CH₂—CH₂—NH₂ (beta-Ala residue),        —CO—CHCH₃—NH₂ (D- and/or L-alpha-Ala residue),        —CO-(pyrrolidine-2-yl) (D- and/or L-Pro residue),        2-amino-2-carbonyl-propane (2-amino-isobutyric acid/Aib        residue), 4-carbonyl-1H-piperidine, 3-carbonyl-1H-piperidine,        R-(3-carbonyl-1H-piperidine), S-(3-carbonyl-1H-piperidine),        2-carbonyl-1H-piperidine, R-(2-carbonyl-1H-piperidine),        S-(2-carbonyl-1H-piperidine), 1-amino-2-carbonyl-benzene,        carbonyl-cyclohexane, 2-acetyl-pyridine, 3-acetyl-pyridine,        4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine,        4-propionyl-pyridine, (R-1-amino)-2-carbonyl-cyclohexane,        (S-1-amino)-2-carbonyl-cyclohexane, 2-carbonyl-1H-imidazole,        2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine,        2-amino-3-carbonyl-pyridine, 2-carbonyl-pyrazine,        2-carbonyl-4-hydroxy-1H-pyrrolidine,        4-carbonyl-1H,3H-diazacyclohexane, methylsulfonyl,        phenylsulfonyl, 1-carbonyl-1-amino-2-phenylethane, phenylmethyl,        1-carbonyl-4-azide-benzene, 2-carbonyl-2,5-dihydro-1H-pyrrole,        2-carbonyl-piperazine, 2-carbonyl-1H-pyrrolidine, 2-aminoethane,        carbonyl-benzene, 2-carbonyl-pyrazine, 3-carbonyl-pyrazine,        4-carbonyl-oxacyclohexane, 4-methyl-phenylsulfonyl,        phenylmethyl-sulfonyl    -   R6 is a hydrogen atom; and    -   m is 0;

that can be used for the manufacture of a medicament for the treatmentor prophylaxis of physiological and/or pathophysiological conditions inmammals that are mediated by GHS receptors.

In a preferred embodiment compounds according to above formula (I) areprovided, where

-   -   R3 is selected from the group consisting of —CH₂—CO—CH₂-phenyl,        —(CH₂)₂—CO—CH₂-phenyl, —CH₂—CO—NH₂, —(CH₂)₂—CO—NH₂, —CH₂—CO—OH,        —(CH₂)₂—CO—OH, —(CH₂)₃—NH—C(NH)—NH₂, —CH₂—SH, —(CH₂)₂—S—CH₃;

that can be used for the manufacture of a medicament for the treatmentor prophylaxis of physiological and/or pathophysiological conditions inmammals that are mediated by GHS receptors.

In another preferred embodiment compounds according to above formula (I)are provided, where

-   -   R5 is selected from the group consisting of hydrogen atom,        methylsulfonyl, phenylsulfonyl, carbonyl-cyclohexane,        (R-1-amino)-2-carbonyl-cyclohexane,        (S-1-amino)-2-carbonyl-cyclohexane, 2-carbonyl-pyridine,        3-carbonyl-pyridine, 4-carbonyl-pyridine, 2-acetyl-pyridine,        3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine,        3-propionyl-pyridine, 4-propionyl-pyridine,        2-amino-3-carbonyl-pyridine, 2-carbonyl-1H-imidazole,        2-carbonyl-pyrazine, 4-carbonyl-1H,3H-diazacyclohexane;

that can be used for the manufacture of a medicament for the treatmentor prophylaxis of physiological and/or pathophysiological conditions inmammals that are mediated by GHS receptors.

In a further aspect, the object of the invention has surprisingly beenachieved by providing novel triazole compounds selected from the groupconsisting of:

compound 1(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 2(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 3(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 4(R)—N-(1-(5-benzyl-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 5(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 6(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 7(R)—N-(1-(4-(3-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 8(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 9(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 10(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 11(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 12(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 13(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 14(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 15(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 16(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 17(R)—N-(1-(4,5-bis(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 18(S)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 20(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 21(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,5-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 22(R)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-thiazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 23(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 24(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-(3-(1H-indol-3-yl)propyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 25(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2-methoxy)benzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 26(R)—N-(1-(4-(2-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-3-yl)-2-amino-2-methylpropanamide,

compound 27(R)—N-(2-(1H-indol-3-yl)-1-(4-(naphthalen-1-ylmethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 28(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,4-dichlorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 29(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-fluorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 30(R)—N-(1-(4-(4-fluorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 31(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 32(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,

compound 33(R)—N-(1-(4-(4-methylbenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 34(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 36(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,

compound 37(R)—N-(1-(4-(4-methylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 38(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide,

compound 39(R)—N-(1-(5-benzyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 40(2S,4R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-hydroxypyrrolidine-2-carboxamide,

compound 41(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,

compound 42(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,

compound 43(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 44(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 45(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 46(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 47(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 48(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,

compound 49(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,

compound 50(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,

compound 51(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 52(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,24-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide,

compound 53(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)cyclohexanecarboxamide,

compound 54(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 56(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-aminopropanamide,

compound 57(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide,

compound 58(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-yl)acetamide,

compound 59(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-(pyridin-3-yl)propanamide,

compound 60(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 61(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 62(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 63(R)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,

compound 64(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 65(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,

compound 66(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,

compound 67(R)—N-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,

compound 68(S)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 69(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,

compound 70(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 71(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,

compound 72(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,

compound 73(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 74(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,

compound 75(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,

compound 76(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,24-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,

compound 77(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,

compound 78(R)—N-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,24-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,

compound 79(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 80(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 81(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,

compound 82(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 83(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide

compound 84(R)—N-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,

compound 85(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,

compound 86(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-cis-aminocyclohexanecarboxamide,

compound 87(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,

compound 88(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,

compound 89(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 90(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 91(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 92(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 93(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide,

compound 94(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(thiophen-2-ylmethyl)-4H-1,24-triazol-3-yl)ethyl)piperidine-4-carboxamide,

compound 95(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 96(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 97(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 98(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 99(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(2,4-dimethoxybenzyl)-4H-1,2-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 100(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 101(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 102(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 103(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 104(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 105(R)—N-(1-(5-benzyl-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 106(R)—N-(1-(5-benzyl-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 107(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 108(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 109(R)—N-(1-(4,5-dibenzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 110(R)—N-(1-(5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 111(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 112(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 113(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 114(R)—N-(1-(4-(4-bromobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 115(R)—N-(1-(4-(2-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 116(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 117(R)—N-(1-(4,5-diphenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 118(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 119(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,

compound 120(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide,

compound 121(R)—N-(1-(4-(4-fluorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 122(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 124(R)—N-(1-(4-(4-methylbenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 125(S)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 126(S)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 128N—((R)-1-(4-(4-nitrobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 129(S)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 130(R)—N-(1-(4-(4-methoxyphenethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 131(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 135N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,

compound 136N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide,

compound 137(2R)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,

compound 132(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 133(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-3-carboxamide,

compound 134(S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 138N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 139N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopyridine-3-carboxamide,

compound 140(2S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide,

compound 141N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,

compound 142N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide,

compound 143(2S)—N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 144N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2-aminoacetamide,

compound 145N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 146N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide,

compound 147N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 148N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 149N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,

compound 150(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,

compound 152N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,

compound 153N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-trans-aminocyclohexanecarboxamide,

compound 154N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-yl)acetamide,

compound 155(3S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,

compound 156N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide,

compound 157N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 158N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 159N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide,

compound 160N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,

compound 161N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)pyrazine-2-carboxamide,

compound 162N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-aminoacetamide,

compound 163N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide,

compound 164N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 165N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-acetamide,

compound 166N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 167N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 168N—((R)-1-(5-(4-methoxybenzyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 169N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 170N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-acetamide,

compound 171(R)-benzyl-3-(2-aminoisobutyramido)-3-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-propanoate,

compound 172N—((R)-1-(5-benzyl-4-((pyridin-3-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 173N—((R)-1-(4-benzyl-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 174N—((R)-2-(1H-indol-3-yl)-1-(4-methyl-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide,

compound 175N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 176N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)benzamide,

compound 177(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-phenylmethanesulfonylamine,

compound 178(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine,

compound 179N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 180N-1-((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)ethane-1,2-diamine,

compound 181N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 182N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,

compound 183N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,

compound 184N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-tetrahydro-2H-pyran-4-carboxamide,

compound 185N—((R)-1-(5-((1H-indol-3-yl)methyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,

compound 186(2S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-3-phenylpropanamide,

compound 187(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine,

compound 188N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-azidobenzamide,

compound 189N-benzyl-(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,

compound 190(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2,5-dihydro-1H-pyrrole-2-carboxamide,

For the avoidance of doubt, if chemical name and chemical structure ofthe above illustrated compounds do not correspond by mistake, thechemical structure is regarded to unambigously define the compound.

In a preferred embodiment these compounds can be used for themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions in mammals that aremediated by GHS receptors.

In a further preferred embodiment all triazole compounds as illustratedherein, i.e. generically (by above formula (I) and different R radicals)and explicitly, in the following referred to as the compounds of the(present) invention, can be used for the manufacture of a medicament forthe treatment or prophylaxis of physiological and/or pathophysiologicalconditions in mammals that are mediated by GHS receptors and where thetreatment is achieved by modulation of GHS receptors.

In yet another preferred embodiment all compounds of the invention areantagonists of GHS receptors.

More preferably, antagonists of GHS receptors are compounds selectedfrom the group consisting of:

compound 1, 3, 12, 13, 14, 18, 20, 22, 23, 33, 36, 37, 38, 41, 46, 47,48, 49, 50, 51, 52, 53, 57, 58, 59, 60, 61, 63, 64, 65, 66, 68, 69, 70,71, 72, 73, 74, 75, 76, 77, 79, 80, 82, 85, 86, 87, 88, 89, 90, 91, 93,101, 102, 109, 114, 116, 119, 134, 135, 136, 137, 138, 139, 140, 145,146, 147, 148, 150, 152, 153, 154, 156, 157, 159, 160, 161, 164, 171,174, 176, 178, 179, 182, 184, 186, 188 and/or compound 190.

In yet a further preferred embodiment all compounds of the invention areagonists of GHS receptors.

More preferably, agonists of GHS receptors are compounds selected fromthe group consisting of:

compound 2, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 17, 19, 21, 24, 25, 26,27, 28, 29, 30, 31, 32, 34, 39, 40, 42, 43, 44, 45, 54, 55, 56, 62, 67,78, 81, 83, 84, 87, 92, 94, 99, 103, 104, 105, 106, 107, 108, 110, 111,115, 117, 118, 121, 122, 124, 130, 131, 142, 155, 158, 163, 173, 175,180, 181, 183, 185 and/or compound 187.

The terms indicated for explanation of the above compounds of formula(I) always, unless indicated otherwise in the description or in theclaims, have the following meanings:

The term substituted means that the corresponding radical or group hasone or more substituents. Where a radical has a plurality ofsubstituents, and a selection of various substituents is specified, thesubstituents are selected independently of one another and need not beidentical. The term unsubstituted means that the corresponding group hasno substituent. The term optionally substituted means that thecorresponding group is either unsubstituted or substituted by one ormore substituents. The term substituted by up to 3 substituents meansthat the corresponding radical or group is substituted either by one orby two or three substituents.

The term alkyl includes for the purposes of this invention acyclicsaturated hydrocarbons having C1-C12 carbon atoms, which may bestraight-chain or branched. The term alkyl preferably stands for alkylchains of 1 to 8, particularly preferably 1 to 6, carbon atoms. Examplesof suitable alkyl radicals are methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl. sec-butyl, tert-butyl, n-pentyl, tert-pentyl, 2- or3-methyl-pentyl, n-hexyl, isohexyl, n-heptyl, n-octyl, n-nonyl, n-decyl,n-undecyl, n-dodecyl.

The term cycloalkyl stands for a saturated or partially unsaturatednon-aromatic cyclic hydrocarbon group/radical, containing 1 to 3 rings,including monocyclic alkyl, bicyclic alkyl and tricyclic alkyl, andcontaining a total of 3 to 20 carbon atoms forming the rings, preferably3 to 10, most preferably (C3-C8)-cycloalkyl. Examples of suitablecycloalkyl radicals are cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclohexenyl,cyclopentenyl, cyclooctadienyl.

The term cycloalkylalkyl refers to a radical in which the cycloalkylgroup is linked via an alkyl group, where the alkyl and cycloalkylgroups have the meanings defined herein, preferably a(C3-C8)-cycloalkyl-(C1-C4)-alkyl radical. Examples thereof arecyclopropylmethyl, cyclohexylmethyl, cyclopentylethyl,cyclohexenylethyl.

The term alkenyl includes for the purposes of this invention acyclicunsaturated or partially unsaturated hydrocarbons having C2-C12 carbonatoms, which may be straight-chain or branched and contain one or moredouble bonds. The term alkenyl preferably stands for alkenyl chains of 2to 8, particularly preferably 2 to 6, carbon atoms. Examples are vinyl,propenyl, butenyl, pentenyl, hexenyl, and octadienyl and the like.

The term alkynyl refers to acyclic unsaturated or partially unsaturatedhydrocarbons having C2-C12 carbon atoms, which may be straight-chain orbranched and contain one or more triple bonds. The term alkynylpreferably stands for alkynyl chains of 2 to 8, particularly preferably2 to 6, carbon atoms. Examples are propynyl, butynyl, pentynyl, hexynyl.

The term aryl refers to aromatic hydrocarbon systems having 3 to 14,preferably 5 to 14, carbon atoms, which may also be fused to furthersaturated, (partially) unsaturated or aromatic cyclic systems. Examplesof aryl are inter alia phenyl, biphenyl, naphthyl and anthracenyl, butalso indanyl, indenyl, or 1,2,3,4-tetrahydronaphthyl.

The term heteroaryl refers to a 5-, 6- or 7-membered cyclic aromaticradical which comprises at least 1, where appropriate also 2, 3, 4 or 5heteroatoms, preferably nitrogen, oxygen and/or sulfur, where theheteroatoms are identical or different. The number of nitrogen atoms ispreferably between 0 and 3, and that of the oxygen and sulfur atoms isbetween 0 and 1. The term heteroaryl also includes systems in which thearomatic cycle is part of a bi- or polycyclic system, such as were thearomatic cycle is fused to an aryl, cycloalkyl, heteroaryl orheterocyclyl group as defined herein via any desired and possible ringmember of the heteroaryl radical. Examples of heteroaryl includepyrrolyl, thienyl, furyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl,isoxazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl,quinolinyl, and isoquinolinyl.

The terms arylalkyl and heteroarylalkyl refer to radicals in which thearyl or heteroaryl radical is linked via an alkyl group, where thealkyl, aryl and heteroaryl groups have the meanings defined herein.Preferred arylalkyl groups are phenyl-(C₁-C₄)-alkyl radicals, preferablybenzyl or phenylethyl radicals. Preferred heteroarylalkyl groups areindolyl-(C₁-C₄)-alkyl radicals, preferably 1H-indole-3-yl-methyl or2(1H-indole-3-yl)-ethyl.

The term heterocyclyl refers to a mono- or polycyclic system of 3 to 14,preferably 5 or 6 to 14 ring atoms which may be exclusively carbonatoms. However, the cyclic system may also comprise 1, 2, 3, 4, or 5heteroatoms, in particular nitrogen, oxygen and/or sulfur. The cyclicsystem may be saturated, mono- or polyunsaturated but may not bearomatic. In the case of a cyclic system consisting of at least tworings the rings may be fused or spiro- or otherwise connected. Theheterocyclyl radical may be attached at any carbon or heteroatom whichresults in the creation of a stable structure. Examples includepyrrolidinyl, thiapyrrolidinyl, piperidinyl, piperazinyl,oxapiperazinyl, oxapiperidinyl and oxadiazolyl.

The term heterocyclylalkyl refers to radicals in which the heterocyclylgroup is linked via an alkyl group, where the alkyl and heterocyclylgroups have the meanings defined herein.

The terms alkylsulfonyl, arylsulfonyl and arylalkylsulfonyl refer toradicals in which the alkyl, aryl or arylalkyl group is linked via a—SO₂— group, where the alkyl, aryl and arylalkyl groups have themeanings defined herein. Examples are methylsulfonyl and phenylsulfonyl.

The term halogen, halogen atom or halogen substituent (Hal-) refers toone, where appropriate, a plurality of fluorine (F, fluoro), bromine(Br, bromo), chlorine (Cl, chloro), or iodine (I, iodo) atoms. Thedesignations dihalogen, trihalogen and perhalogen refer respectively totwo, three and four substituents, where each substituent can be selectedindependently from the group consisting of fluorine, chlorine, bromineand iodine. Halogen preferably means a fluorine, chlorine or bromineatom.

The term natural alpha-amino acid side chain for the purpose of thepresent invention refers to all side chains of the known 20proteinogenic alpha-amino acids as well as to side chains of naturallyoccurring (i.e. in any biological systems) alpha-amino acids, such asfor instance selenocystein, pyrrolysine, citrulline, ornithine,homocysteine, N-methylariginine, N-acetyllysine, gamma-carboxyglutamate,5-hydroxylysine, 3-methylhistidine and/or N,N,N,-trimethyllysine. Inthis connection side chain refers to the residue that is attached to thealpha-carbon atom, e.g. methyl in case of an Ala side chain or benzyl incase of a Phe side chain.

The term unnatural alpha amino acid side chain for the purpose of thepresent invention refers to all side chains of known alpha-amino acidsthat are not proteinogenic nor are known to occur naturally (i.e. in anybiological systems). Examples are norleucine, cyclohexylglycine,2-naphthylalanine, substituted alpha-amino acids (e.g. halogensubstituted Tyr or Phe) as well as protected alpha-amino acid sidechains, where a protection group such as Fmoc, Boc, Z, CBZ, Aloc,trityl, acetyl and/or benzyl is directly attached/reacted to afunctionalization (e.g. amino, hydroxy and/or carboxy residue). In thisconnection side chain is referred to as for natural alpha amino acidside chains.

Above embodiments of radicals R1 to R10 that possess functionalization(e.g. amino, hydroxy and/or carboxy residues), such as alkyl-CO—NH₂,-alkyl-CO—OH, -alkyl-NH₂, -alkyl-NH—C(NH)—NH₂, —CO—C*(R9R10)-NH₂,—CO—CH₂—C*(R9R10)-NH₂, —CO—C*(R9R10)-CH₂—NH₂ and/or2-amino-2-carbonyl-propane (2-amino-isobutyric acid/Aib residue), may beprotected with protection groups as mentioned above. Such protectiongroup carrying embodiments are regarded as belonging to/within the scopeand spirit of the invention.

All stereoisomers of the compounds of the invention are contemplated,either in a mixture or in pure or substantially pure form. The compoundsof the present invention can have asymmetric centers at any of thecarbon atoms including any one of the R radicals. Consequently,compounds of the invention can exist in the form of their racemates, inthe form of the pure enantiomers and/or diastereomers or in the form ofmixtures of these enantiomers and/or diastereomers. The mixtures mayhave any desired mixing ratio of the stereoisomers. All these differentstereochemical forms and mixtures are within the scope of the presentinvention.

Thus, for example, the compounds of the invention which have one or morecenters of chirality and which occur as racemates or as diastereomermixtures can be fractionated by methods known per se into their opticalpure isomers, i.e. enantiomers or diastereomers. The separation of thecompounds of the invention can take place by column separation on chiralor nonchiral phases or by recrystallization from an optionally opticallyactive solvent or with use of an optically active acid or base or byderivatization with an optically active reagent such as, for example, anoptically active alcohol, and subsequent elimination of the radical.

Where possible, the compounds of the invention may be in the form of thetautomers.

It is likewise possible for the compounds of the invention to be in theform of any desired prodrugs such as, for example, esters, carbonates orphosphates, in which cases the actually biologically active form isreleased only through metabolism. Any compound that can be converted invivo to provide the bioactive agent (i.e. a compound of the invention)is a prodrug within the scope and spirit of the invention.

Various forms of prodrugs are well known in the art and are describedfor instance in:

-   -   (i) The Practice of Medicinal Chemistry (Wermuth C G et al.,        Chapter 31, Academic Press 1996);    -   (ii) Design of Prodrugs (editor: Bundgaard H, Elsevier 1985);        and    -   (iii) A Textbook of Drug Design and Development        (Krogsgaard-Larson P and Bundgaard H, eds., Chapter 5: 113-191,        Harwood Academic Publishers 1991).

Said references are incorporated herein by reference.

It is further known that chemical substances are converted in the bodyinto metabolites which may where appropriate likewise elicit the desiredbiological effect—in some circumstances even in more pronounced form.

Any biologically active compound that was converted in vivo bymetabolism from any compound of the invention is a metabolite within thescope and spirit of the invention.

The compounds of the invention can, if they have a sufficiently basicgroup such as, for example, a primary, secondary or tertiary amine, beconverted with inorganic and organic acids into salts. Thepharmaceutically acceptable salts of the compounds of the invention arepreferably formed with hydrochloric acid, hydrobromic acid, iodic acid,sulfuric acid, phosphoric acid, methanesulfonic acid, p-toluenesulfonicacid, carbonic acid, formic acid, acetic acid, sulfoacetic acid,trifluoroacetic acid, oxalic acid, malonic acid, maleic acid, succinicacid, tartaric acid, racemic acid, malic acid, embonic acid, mandelicacid, fumaric acid, lactic acid, citric acid, taurocholic acid, glutaricacid, stearic acid, glutamic acid or aspartic acid. The salts which areformed are, inter alia, hydrochlorides, chlorided, hydrobromides,bromides, iodides, sulfates, phosphates, methanesulfonates, tosylates,carbonates, bicarbonates, formates, acetates, sulfoacetates, triflates,oxalates, malonates, maleates, succinates, tartrates, malates,embonates, mandelates, fumarates, lactates, citrates, glutarate,stearate, aspartates and glutamates. The stoichiometry of the saltsformed from the compounds of the invention may moreover be an integralor non-integral multiple of one.

The compounds of the invention can, if they contain a sufficientlyacidic group such as, for example, the carboxy, sulfonic acid,phosphoric acid or a phenolic group, be converted with inorganic andorganic bases into their physiologically tolerated salts. Examples ofsuitable inorganic bases are ammonium, sodium hydroxide, potassiumhydroxide, calcium hydroxide, and of organic bases are ethanolamine,diethanolamine, triethanolamine, ethylenediamine, t-butylamine,t-octylamine, dehydroabietylamine, cyclohexylamine,dibenzylethylene-diamine and lysine. The stoichiometry of the saltsformed from the compounds of the invention can moreover be an integralor non-integral multiple of one.

It is likewise possible for the compounds of the invention to be in theform of their solvates and, in particular, hydrates which can beobtained for example by crystallization from a solvent or from aqueoussolution. It is moreover possible for one, two, three or any number ofsolvate or water molecules to combine with the compounds of theinvention to give solvates and hydrates.

It is known that chemical substances form solids which exist indifferent order states which are referred to as polymorphic forms ormodifications. The various modifications of a polymorphic substance maydiffer greatly in their physical properties. The compounds of theinvention can exist in various polymorphic forms, and certainmodifications may moreover be metastable. All these polymorphic forms ofthe compounds of the invention are to be regarded as belonging to theinvention.

The triazole derivatives (compounds of the invention) as illustratedherein are ghrelin analogue ligands of GHS receptors. Thus, theaforementioned compounds of the invention are suitable for the treatmentor prophylaxis of physiological and/or pathophysiological conditionsmediated by GHS receptors and/or physiological and/or pathophysiologicalconditions which can be influenced by modulation of these receptors, andthus prevented, treated and/or alleviated.

For the purpose of the present invention, the term treatment is alsointended to include prophylactic treatment or alleviation.

The term ghrelin analogue ligand or ligand is intended to refer for thepurposes of the present invention to every compound which binds in anyway to a receptor (the receptors in the present invention being GHSreceptors) and induces either activation, inhibition and/or anotherconceivable effect at this receptor. The term ghrelin analogue ligand orligand thus includes agonists, antagonists, partialagonists/antagonists, inverse agonists and other ligands which cause aneffect at the receptor which is similar to the effect of agonists,antagonists, partial agonists/antagonists or inverse agonist.

For the purpose of the present invention, the term GHS receptorantagonist or antagonist of GHS receptors refers to compounds of theinvention that bind to GHS receptors but do not elicit a properactivation of the receptors as assessed by recording an increase ofintracellular calcium which is characteristic for activation ofG-protein coupled receptors (GPCRs).

The ability to properly activate the receptors is assessed for anycompound of the invention by comparing the degree of activation(increase of intracellular calcium) of GHS-R 1a by the compound to betested (at 10⁻⁶ M concentration) to the degree of activation (increaseof intracellular calcium) of GHS-R 1a by 10⁻⁶ M ghrelin (100%) and tothe basal level (0%). Such assessment can be readily performed by theskilled artisan due to his expert knowledge. The output is a percentagevalue for each compound to be tested.

Any compound of the invention that does not show a degree of activation(increase of intracellular calcium) of GHS-R 1a of at least 20% asassessed in accordance with above specification is regarded as noteliciting a proper activation and therefore as GHS receptor antagonist.Preferably such compounds do show an antagonizing effect(counteraction/decrease) on ghrelin and/or other GHS stimulatedintracellular calcium increase, prevent such stimulation or even act asinverse agonists (an inverse agonists is an ligand which binds to thesame receptor binding-site as an agonist or antagonist but causes aninhibition of the basal/constitutive activity of the receptor, inprinciple an agonists with a negative intrinsic activity). Suchcompounds may furthermore exhibit an inhibitory activity on GH secretionand/or on other physiological or pathophysiological conditions oreffects, such as food intake or lipogenesis. Their effects may bedissociated. Thus, they may have no impact at all on GH secretion whileinhibiting other physiological effects. They may even stimulate otherphysiological effects.

For the purpose of the present invention, the term GHS receptor agonistor agonist of GHS receptors refers to compounds of the invention thatbind to GHS receptors and elicit a proper activation of the receptor asassessed by recording an increase of intracellular calcium which ischaracteristic for activation of G-protein coupled receptors.

Any compound of the invention that shows a degree of activation(increase of intracellular calcium) of GHS-R 1a of at least 20% asassessed in accordance with above specification is regarded as elicitinga proper activation and therefore as GHS receptor agonist. Suchcompounds may mimic the effects of ghrelin and/or GHS on GH secretionand for instance food intake or lipogenesis. Like for antagonists, theeffects of agonist compounds may be dissociated from the GH secretoryeffect. Such compounds may even antagonize (counteract/decrease) ghrelinand/or other GHS stimulated intracellular calcium increase.

The term GHS receptor or GHS-R is intended to comprise for the purposesof the present invention receptors that bind at least one known peptidyland/or non-peptidyl GHS and/or ghrelin. The term GHS receptor or GHS-Ris also intended to comprise different GHS binding sites in the varioustissues and/or organs as illustrated herein, that bind at least oneknown peptidyl and/or non-peptidyl GHS and/or ghrelin and which areprobably not yet characterized GHS-R subtypes.

Binding of a given known peptidyl and/or non-peptidyl GHS and/or ghrelincan be easily verified by the skilled artisan on the basis of his expertknowledge, e.g. by appropriate binding assays which represent onlyroutine experimentation.

Such GHS receptors may be stimulated/activated by ghrelin (ghrelinresponsive) or may not be stimulated/activated by ghrelin (ghrelinnon-responsive)—with regard to both acylated and non-acylated ghrelin,respectively. Stimulation/activation of such receptors may cause butdoes not compulsorily have to elicit GH production and/or GH secretionand/or increase GH plasma levels.

Preferably such GHS receptors are selected from the group consisting ofGHS type 1 receptor, GHS-R 1a, GHS-R 1b, motilin receptor, motilinreceptor 1a, neurotensin receptor, TRH receptor, GPR38 (FM1), GPR39(FM2), FM3, GHS binding site, GHS-R subtype, cardiac GHS-R, mammaryGHS-R.

More preferably, such GHS receptors are selected from the groupconsisting of GHS type 1 receptor, GHS-R 1a, GHS-R 1b and mostpreferably are GHS-R 1a.

As discussed herein, GHS receptors (including GHS binding sites andGHS-R sub-types) are known to be concentrated in thehypothalamus-pituitary area but also appear to be distributed in othercentral and peripheral tissues. Furthermore, they are also expressed invarious tumoral tissues, even in tumoral tissues from organs that do notexpress these receptors under physiological conditions.

For the purposes of the present invention, all these GHS receptor(including GHS binding sites and GHS-R subtypes) expressing organsand/or tissues are intended to be comprised by the scope of the presentinvention. Expression of GHS receptors (including GHS binding sites andGHS-R subtypes) in a given organ and/or tissue can be easily verified bythe skilled artisan on the basis of his expert knowledge, e.g. byappropriate molecular biologic assays, such as immunofluorescence orimmunoprecipitation assays, which represent only routineexperimentation.

Preferably, such GHS receptors are located in tissues and/or organsselected from the group consisting of endocrine tissue, exocrine tissue,peripheral tissue, adipose/fat tissue, brain, hypothalamus, thalamus,hippocampus, striatum, cortex, pituitary, central nervous system, spinalcord, gland, adrenal gland, thyroid gland, salivary gland, mammarygland, neuron, bowel, intestine, stomach, heart, liver, pancreas,kidney, bile, gall, bladder, prostate, spleen, muscle, skeletal muscle,aorta, artery, vein, immune cell, leukocyte, lymphocyte, T cell, B cell,granulocyte, monocyte, macrophage, dendritic cell, mast cell, NK cell,neutrophil, eosinophil, basophil, lymph node, bone, bone marrow, tonsil,thymus, placenta, testes, ovary, uterus, lung, adipocyte, tumor/cancercell, carcinoma cell, prostate cancer cell, thyroid cancer cell, lungcancer cell, breast cancer cell.

As illustrated supra, the compounds of the invention are ghrelinanalogue ligands of GHS receptors. They can be administered to variousmammalian species, including human, for the treatment or prophylaxis ofphysiological and/or pathophysiological condition in such mammals.

For the purpose of the present invention, all mammalian species areregarded as being comprised. Preferably, such mammals are selected fromthe group consisting of human, domestic animals, cattle, livestock,pets, cow, sheep, pig, goat, horse, pony, donkey, hinny, mule, hare,rabbit, cat, dog, guinea pig, hamster, rat, mouse. More preferably, suchmammals are human.

The compounds of the invention being non-peptidic ghrelin analogueligands of GHS receptors are surprisingly characterized by a strongbinding affinity to such receptors. Such compounds for instance maypreferably exhibit an IC₅₀ value of less than 1000 nM for binding toGHS-R 1a. More preferably, such compounds may exhibit an IC₅₀ value ofless than 500 nM, even more preferably of less than 300 nM and mostpreferably of less than 100 nM for binding to GHS-R 1a.

Due to their surprisingly strong receptor binding, the compounds of theinvention can be advantageously administered at lower doses compared toother less potent binders while still achieving equivalent or evensuperior desired biological effects. In addition, such a dose reductionmay advantageously lead to less or even no medicinal adverse effects.Further, the high binding specificity of the compounds of the inventionmay translate into a decrease of undesired side effects on its ownregardless of the dose applied.

Furthermore, the compounds of the invention, being of non-peptidicnature, are resistant to degradation by enzymes of the gastrointestinaltract. Hence, they offer the advantage to be given by oral route. Theysurprisingly display an improved metabolic stability and/or an improvedbioavailability. Hence, again an advantageous dose reduction may beachievable which may cause less or even no side effects.

The compounds of the invention can either be antagonists or agonists ofGHS receptors as illustrated and defined herein.

GHS receptor antagonists of the present invention can for instance beemployed for the inhibition of GHS receptors stimulated by ghrelinand/or other GHS thus decreasing and/or blocking GH production and/orsecretion and/or GH plasma levels. In addition, such GHS receptorantagonists may also be employed for the inhibition or prevention ofphysiological or pathophysiological effects of ghrelin which are notrelated to GH production and/or GH secretion.

Therefore, GHS receptor antagonists of the present invention aresuitable for the treatment and/or prophylaxis of various physiologicaland pathophysiological conditions as disclosed herein, in particular forthe short-, medium- and/or long term regulation of energy balance, theshort-, medium- and/or long term regulation (stimulation and/orinhibition) of food intake, the treatment of adipogenesis, adiposityand/or obesity, body weight gain and/or reduction and the treatment oftumor cell proliferation.

In contrast, GHS receptor agonists of the present invention can forinstance be employed for the activation of GHS receptors andstimulation/increase of GH production and/or GH secretion and would thushave similar effects or uses as growth hormone itself, ghrelin and/orknown GHS.

Thus, GHS receptor agonists of the present invention are suitable forthe treatment and/or prophylaxis of various physiological andpathophysiological conditions as disclosed herein, in particular forgrowth retardation, cachexia, inflammation, inflammatory effects,gastric postoperative ileus, postoperative ileus and/or gastrectomy(ghrelin replacement therapy).

For the purpose of the present invention, all physiological and/orpathophysiological conditions are intended to be comprised that areknown to be mediated by GHS receptors.

Preferably, these physiological and/or pathophysiological conditions areselected from the group consisting of acute fatigue syndrome and muscleloss following election surgery, adipogenesis, adiposity, age-relateddecline of thymic function, age-related functional decline (ARFD) in theelderly, aging disorder in companion animals, Alzheimer's disease,anorexia (e.g. associated with cachexia or aging); anxiety, bloodpressure (lowering), body weight gain/reduction, bone fracture repair(acceleration), bone remodeling stimulation, cachexia and protein lossreduction due to chronic illness such as cancer or AIDS, cardiacdysfunctions (e.g. associated with valvular disease, myocarialinfarction, cardiac hypertrophy or congestive heart failure),cardiomyopathy, cartilage growth stimulation, catabolic disorders inconnection with pulmonary dysfunction and ventilator dependency,catabolic side effects of glucocorticoids, catabolic state of aging,central nervous system disorders (in combination with antidepressants),chronic dialysis, chronic fatigue syndrome (CFS), cognitive functionimprovement (e.g. in dementia, Alzheimer's disease), complicatedfractures (e.g. disctraction osteogenesis), complications associatedwith transplantation, congestive heart failure (alone/in combinationwith corticotropin releasing factor antagonists), Crohn's disease andulcerative colits, Cushing's syndrome, dementia, depressions, short-,medium- and/or long-term regulation of energy balance, short-, medium-and/or long-term regulation of food intake (stimulation and/orinhibition), fraility (e.g. in elderly humans), gastrectomy (ghrelinreplacement therapy), gastric postoperative ileus, glycemic controlimprovement, growth hormone release stimulation in the elderly, growthhormone replacement in stressed patients, growth promotion in livestock,growth retardation associated with the Prader-Willi syndrome andTurner's syndrome, growth retardation in connection with Crohn'sdisease, growth retardation, hair/nail growth maintenance, hipfractures, hunger, hypercortisolism, hyperinsulinemia includingnesidioblastosis, hypothermia, immune deficiency in individuals with adepressed T4/T8 cell ratio, immune response improvement to vaccination,immune system stimulation in companion animals, immune systemstimulation, immunosuppression in immunosuppressed patients,inflammation or inflammatory effects, inflammatory bowel disease,insulin resistance in the heart, insulin resistance in type 2 diabeticpatients, insulin resistance including NIDDM, diabetes, diabetes type I,diabetes type II, intrauterine growth retardation, irritable bowelsyndrome, lipodystrophy (e.g. HIV-induced), metabolic homeostasismaintenance, milk production increase in livestock, muscle mass/strengthincrease, muscle mobility improvement, muscle strength improvement,muscle strength/function maintenance in elderly humans, muscularatrophy, musculoskeletal impairment (e.g. in elderly), Noonan'ssyndrome, obesity and growth retardation associated with obesity,osteoblast stimulation, osteochondrodysplasias, osteoporosis, ovulationinduction (adjuvant treatment), physiological short stature includinggrowth hormone deficient children, postoperative ileus, proteincatabolic response attenuation after major surgery/trauma, proteinkinase B activity enhancement, psychosocial deprivation, pulmonarydysfunction and ventilator dependency, pulmonary function improvement,pulsatile growth hormone release induction, recovery of burn patientsand reducing hospitalization of burn patients (acceleration), renalfailure or insufficiency resulting from growth retardation, renalhomeostasis maintenance in the frail elderly, sarcopenia, schizophrenia,sensory function maintenance (e.g. hearing, sight, olefaction andtaste), short bowel syndrome, short stature associated with chronicillness, skeletal dysplasia, skin thickness maintenance, sleepdisorders, sleep quality improvement, thrombocytopenia, thymicdevelopment stimulation, tooth repair or growth, tumor cellproliferation, ventricular dysfunction or reperfusion events, wasting inconnection with AIDS, wasting in connection with chronic liver disease,wasting in connection with chronic obstructive pulmonary disease (COPD),wasting in connection with multiple sclerosis or other neurodegenerativedisorders, wasting secondary to fractures, wool growth stimulation insheep, wound healing (acceleration), wound healing delay. Morepreferably these physiological and/or pathophysiological conditions areselected from the group consisting of growth retardation, cachexia,short-, medium- and/or long term regulation of energy balance; short-,medium- and/or long term regulation (stimulation and/or inhibition) offood intake; adipogenesis, adiposity and/or obesity; body weight gainand/or reduction; diabetes, diabetes type I, diabetes type II, tumorcell proliferation; inflammation, inflammatory effects, gastricpostoperative ileus, postoperative ileus and/or gastrectomy (ghrelinreplacement therapy).

In a further aspect of the present invention, the compounds of theinvention may be used in combination with at least one additionalpharmacologically active substance.

Such additional pharmacologically active substance may be othercompounds of the present invention and/or other suitable therapeuticagents useful in the treatment and/or prophylaxis of the aforementionedphysiological and/or pathophysiological conditions. The additionalpharmacologically active substance may be an antagonist of GHS receptorsand/or an agonist of GHS receptors depending on the purpose of thecombined use. Selection and combination of the additionalpharmacologically active substance(s) can be easily performed by theskilled artisan on the basis of his expert knowledge and depending onthe purpose of the combined use and physiological and/orpathophysiological conditions targeted.

In a preferred embodiment, the compounds of the invention are used forthe treatment and/or prophylaxis of the aforementioned physiologicaland/or pathophysiological conditions in the form of a medicament, wheresuch medicament comprises at least one additional pharmacologicallyactive substance.

In another preferred embodiment, the compounds of the invention are usedfor the treatment and/or prophylaxis of the aforementioned physiologicaland/or pathophysiological conditions in the form of a medicament, wherethe medicament is applied before and/or during and/or after treatmentwith at least one additional pharmacologically active substance.

The above mentioned suitable therapeutic agents include: GHS,anti-diabetic agents; anti-osteoporosous agents; anti-obesity agents;anti-inflammatory agents; anti-anxiety agents; anti-depressants;anti-hypertensive agents; anti-platelet agents; antithrombotic andthrombolytic agents; cardiac glycosides; cholesterol/lipid loweringagents; mineralocorticoid receptor antagonists; phosphodiesteraseinhibitors; protein tyrosine kinase inhibitors; thyroid mimetics(including thyroid receptor antagonists); anabolic agents; HIV or AIDStherapies; therapies useful in the treatment of Alzheimer's disease andother cognitive disorders; therapies useful in the treatment of sleepingdisorders; anti-proliferative agents; anti-tumor agents; anti-ulcer andgastroesopheageal reflux disease agents; progestin receptor agonists(PRA); estrogen; testosterone; a selective estrogen receptor modulator;a selective androgen receptor modulator; parathyroid hormone; and/orbisphosphonate, and preferably, a suitable therapeutic agents isselected of the group consisting of this agents.

Examples of suitable GHS for use in combination with the compounds ofthe present invention include GHRP-6, GHRP-1 as described in U.S. Pat.No. 4,411,890; and publications WO 89/07110 and WO 89/07111 and B-HT920or growth hormone releasing factor and its analogs or growth hormone andits analogs or somatomedins including IGF-1 and IGF-2 as well as GHSdescribed in WO 01/96300.

Examples of suitable anti-diabetic agents for use in combination withthe compounds of the present invention include biguanides (e.g.metformin), glucosidase inhibitors (e.g. acarbose), insulins (includinginsulin secretagogues or insulin sensitizers), meglitinides (e.g.repaglinide), sulfonylureas (e.g., glimepiride, glyburide andglipizide), biguanide/glyburide combinations (e.g., glucovance),thiozolidinediones (e.g. troglitazone, rosiglitazone and pioglitazone),PPAR-alpha agonists, PPAR-gamma agonists, PPAR alpha/gamma dualagonists, SGLT2 inhibitors, inhibitors of fatty acid binding protein(aP2) such as those disclosed in U.S. Pat. No. 6,548,529, glucagon-likepeptide-1 (GLP-1), and dipeptidyl peptidase IV (DP4) inhibitors.

Examples of suitable anti-osteoporosous agents for use in combinationwith the compounds of the present invention include alendronate,risedronate, raloxifene, calcitonin, non-steroidal progestin receptoragonists, RANK ligand agonists, calcium sensing receptor antagonists,TRAP inhibitors, selective estrogen receptor modulators (SERM), estrogenand AP-1 inhibitors.

Examples of suitable anti-obesity agents for use in combination with thecompounds of the present invention include endocannabinoid receptorantagonists, e.g. CB1 receptor antagonists such as rimonabant(1H-Pyrazole-3-carboxamide,5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-piperidinyl-,monohydrochloride; CAS Registry Number: 158681-13-1; SR-141716A; U.S.Pat. No. 5,624,941), aP2 inhibitors such as those disclosed in U.S. Pat.No. 6,548,529, PPAR gamma antagonists, PPAR delta agonists, andorlistat.

Examples of suitable antinflammatory agents for use in combination withthe compounds of the present invention include prednisone,dexamethasone, Enbrel, cyclooxygenase inhibitors (i.e., COX-1 and/orCOX-2 inhibitors such as NSAIDs, aspirin, indomethacin, ibuprofen,piroxicam, Naproxen, Celebrex, Vioxx), CTLA4-Ig agonists/antagonists,CD40 ligand antagonists, integrin antagonists, alpha4 beta7 integrinantagonists, cell adhesion inhibitors, interferon gamma antagonists,ICAM-1, tumor necrosis factor (TNF) antagonists (e.g., infliximab,OR1384), prostaglandin synthesis inhibitors, budesonide, clofazimine,CNI-1493, CD4 antagonists (e.g., priliximab), p38 mitogen-activatedprotein kinase inhibitors, protein tyrosine kinase (PTK) inhibitors, IKKinhibitors, and therapies for the treatment of irritable bowel syndrome(e.g., zelmac and Maxi-K openers such as those disclosed in U.S. Pat.No. 6,184,231).

Examples of suitable anti-anxiety agents for use in combination with thecompounds of the present invention include diazepam, lorazepam,buspirone, oxazepam, and hydroxyzine pamoate.

Examples of suitable anti-depressants for use in combination with thecompounds of the present invention include citalopram, fluoxetine,nefazodone, sertraline, and paroxetine.

Examples of suitable anti-hypertensive agents for use in combinationwith the compounds of the present invention include beta adrenergicblockers, calcium channel blockers (L-type and T-type; e.g. diltiazem,verapamil, nifedipine, amlodipine and mybefradii), diruetics (e.g.,chlorothiazide, hydrochlorothiazide, flumethiazide, hydroflumethiazide,bendroflumethiazide, methylchlorothiazide, trichloromethiazide,polythiazide, benzthiazide, ethacrynic acid tricrynafen, chlorthalidone,furosemide, musolimine, bumetamide, triamtrenene, amiloride,spironolactone), renin inhibitors, ACE inhibitors (e.g., captopril,zofenopril, fosinopril, enalapril, ceranopril, cilazopril, delapril,pentopril, quinapril, ramipril, lisinopril), AT-1 receptor antagonists(e.g., losartan, irbesartan, valsartan), ET receptor antagonists (e.g.,sitaxsentan, atrsentan and compounds disclosed in U.S. Pat. Nos.5,612,359 and 6,043,265, Dual ET/All antagonist (e.g., compoundsdisclosed in WO 00/01389), neutral endopeptidase (NEP) inhibitors,vasopepsidase inhibitors (dual NEP-ACE inhibitors) (e.g., omapatrilatand gemopatrilat), and nitrates.

Examples of suitable anti-platelet agents for use in combination withthe compounds of the present invention include GPIIb/IIIa blockers(e.g., abciximab, eptifibatide, tirofiban), P2Y12 antagonists (e.g.,clopidogrel, ticlopidine, CS-747), thromboxane receptor antagonists(e.g., ifetroban), aspirin, and PDE-III inhibitors (e.g., dipyridamole)with or without aspirin.

Examples of suitable cardiac glycosides for use in combination with thecompounds of the present invention include digitalis and ouabain.

Examples of suitable cholesterol/lipid lowering agents for use incombination with the compounds of the present invention include HMG-CoAreductase inhibitors [e.g., pravastatin lovastatin, atorvastatin,simvastatin, NK-104 (a.k.a. itavastatin, or nisvastatin or nisbastatin]and ZD-4522 (a.k.a. rosuvastatin, or atavastatin or visastatin)),squalene synthetase inhibitors, fibrates, bile acid sequestrants, ACATinhibitors, MTP inhibitors, lipooxygenase inhibitors, choesterolabsorption inhibitors, and cholesterol ester transfer protein inhibitors(e.g., CP-529414).

Examples of suitable mineralocorticoid receptor antagonists for use incombination with the compounds of the present invention includespironolactone and eplerinone.

Examples of suitable phosphodiesterase inhibitiors for use incombination with the compounds of the present invention include PDE IIIinhibitors such as cilostazol, and PDE V inhibitors such as sildenafil.

Examples of suitable thyroid mimetics for use in combination with thecompounds of the present invention include thyrotropin, polythyroid,KB-130015, and dronedarone.

Examples of suitable anabolic agents for use in combination with thecompounds of the present invention include testosterone and SARMs.

Examples of suitable HIV or AIDS therapies for use in combination withthe compounds of the present invention include indinavir sulfate,saquinavir, saquinavir mesylate, amprenavir, ritonavir, lopinavir,ritonavir/lopinavir combinations, lamivudine, zidovudine,lamivudine/zidovudine combinations, zalcitabine, didanosine, stavudine,and megestrol acetate.

Examples of suitable therapies for treatment of Alzheimer's disease andcognitive disorders for use in combination with the compounds of thepresent invention include donepezil, tacrine, revastigmine, 5HT6, gammasecretase inhibitors, beta secretase inhibitors, SK channel blockers,Maxi-K blockers, and KCNQs blockers.

Examples of suitable therapies for treatment of sleeping disorders foruse in combination with the compounds of the present invention includemelatonin analogs, melatonin receptor antagonists, ML1B agonists, andGABA/NMDA receptor antagonists.

Examples of suitable anti-proliferative agents for use in combinationwith the compounds of the present invention include cyclosporin A,taxol, FK 506, and adriamycin.

Examples of suitable anti-tumor agents for use in combination with thecompounds of the present invention include taxol, adriamycin,epothilones, cisplatin and carboplatin.

Examples of suitable a selective estrogen receptor modulator for use incombination with the compounds of the present invention includetamoxifen and raloxifene.

Examples of suitable a selective androgen receptor modulator for use incombination with the compounds of the present invention include suchdisclosed in Edwards, J. P. et al., Bio. Med. Chem. Let., 9, 1003-1008(1999) and Hamann, L. G. et al., J. Med. Chem., 12, 210-212 (1999).

Examples of suitable a bisphosphonate for use in combination with thecompounds of the present invention include MK-217 (alendronate).

The above other therapeutic agents, when employed in combination withthe compounds of the present invention, may be used, for example, inthose amounts indicated in the Physicians' Desk Reference (PDR) or asotherwise determined by one of ordinary skill in the art.

In a preferred embodiment, the compounds of the invention are used forthe treatment and/or prophylaxis of the aforementioned physiologicaland/or pathophysiological conditions in the form of a medicament, wheresuch medicament comprises as additional pharmacologically activesubstance an endocannabinoid receptor antagonist, preferably a CB1receptor antagonist, most preferably rimonabant(1H-Pyrazole-3-carboxamide,5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-piperidinyl-,monohydrochloride; CAS Registry Number: 158681-13-1; SR-141716A; U.S.Pat. No. 5,624,941) and as compound of the invention a GHS-R antagonist.

In another preferred embodiment, the compounds of the invention are usedfor the treatment and/or prophylaxis of the aforementioned physiologicaland/or pathophysiological conditions in the form of a medicament, wherethe medicament is applied before and/or during and/or after treatmentwith at least one additional pharmacologically active substance, wheresuch additional pharmacologically active substance is an endocannabinoidreceptor antagonist, preferably a CB1 receptor antagonist, mostpreferably rimonabant (1H-Pyrazole-3-carboxamide,5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-piperidinyl-,monohydrochloride; CAS Registry Number: 158681-13-1; SR-141716A; U.S.Pat. No. 5,624,941) and the compound of the invention is a GHS-Rantagonist.

The compounds of the present invention can be administered in a knownmanner. The route of administration may thereby be any route whicheffectively transports the active compound to the appropriate or desiredsite of action, for example orally or non-orally, in particulartopically, transdermally, pulmonary, rectally, intravaginally, nasallyor parenteral or by implantation. Oral administration is preferred.

The compounds of the invention are converted into a form which can beadministered and are mixed where appropriate with pharmaceuticallyacceptable carriers or diluents. Suitable excipients and carriers aredescribed for example in Ullman's Encyclopedia of Technical Chemistry,Vol. 4, (1953), 1-39; Journal of Pharmaceutical Sciences, Vol. 52(1963), 918 et seq.; H. v. Czetsch-Lindenwald, Hilfsstoffe für Pharmazieand angrenzende Gebiete; Pharm. Ind. 2, 1961, 72 et seq.; Dr. H. P.Fiedler, Lexikon der Hilfsstoffe für Pharmazie, Kosmetik and angrenzendeGebiete, Cantor K G, Aulendorf in Württemberg, 1971.

Oral administration can take place for example in solid form as tablet,capsule, gel capsule, coated tablet, granulation or powder, but also inthe form of a drinkable solution. The compounds of the invention can fororal administration be combined with known and ordinarily used,physiologically tolerated excipients and carriers such as, for example,gum arabic, talc, starch, sugars such as, for example, mannitol,methylcellulose, lactose, gelatin, surface-active agents, magnesiumstearate, cyclodextrins, aqueous or nonaqueous carriers, diluents,dispersants, emulsifiers, lubricants, preservatives and flavorings (e.g.essential oils). The compounds of the invention can also be dispersed ina microparticulate, e.g. nanoparticulate, composition.

Non-oral administration can take place for example by intravenous,subcutaneous, intramuscular injection of sterile aqueous or oilysolutions, suspensions or emulsions, by means of implants or byointments, creams or suppositories. Administration as sustained releaseform is also possible where appropriate. Implants may comprise inertmaterials, e.g. biodegradable polymers or synthetic silicones such as,for example, silicone rubber. Intravaginal administration is possiblefor example by means of vaginal rings. Intrauterine administration ispossible for example by means of diaphragms or other suitableintrauterine devices. Transdermal administration is additionallyprovided, in particular by means of a formulation suitable for thispurpose and/or suitable means such as, for example, patches.

The dosage may vary within a wide range depending on type and/orseverity of the physiological and/or pathophysiological condition, themode of administration, the age, gender, bodyweight and sensitivity ofthe subject to be treated. It is within the ability of a skilled workerto determine a pharmacologically effective amount of a compound of theinvention and/or additional pharmacologically active substance.Administration can take place in a single dose or a plurality ofseparate dosages.

A suitable unit dose is, for example, from 0.001 mg to 100 mg of theactive ingredient, i.e. at least one compound of the invention and,where appropriate, at least one additional pharmacologically activesubstance, per kg of a patient's bodyweight.

In another aspect, the present invention relates to a pharmaceuticalcomposition comprising a pharmacologically active amount of at least onetriazole compound selected from the group consisting of: compound 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 124, 125,126, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 152, 153, 154, 155,156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169,170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183,184, 185, 186, 187, 188, 189 and/or compound 190.

In a further aspect, such a pharmaceutical composition may additionallycomprise at least one pharmaceutically acceptable carrier and/orexcipient and/or may comprise at least one further pharmacologicallyactive substance.

In a preferred embodiment, such further pharmacologically activesubstance is an endocannabinoid receptor antagonist, preferably a CB1receptor antagonist, most preferably rimonabant[1H-Pyrazole-3-carboxamide,5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-piperidinyl-,monohydrochloride].

Concerning the pharmaceutical compositions of the invention, at leastone of the triazole compounds as listed above is present in apharmacologically effective amount, preferably in a unit dose, e.g. theaforementioned unit dose, specifically and preferably in anadministration form which makes oral administration possible.Furthermore, reference may be made to that already said in connectionwith the possible uses and administrations of the compounds of theinvention.

General Syntheses Schemes

The compounds of the present invention may be prepared according to thefollowing general synthetic schemes, as well as relevant publishedliterature procedures that are known to the one skilled in the art (e.g.WO 00/54729 and cited references therein).

Exemplary reagents and procedures for these reactions appear hereinafterand in the working examples. Unless otherwise specified, the varioussubstituents (radicals) of the compounds have the meanings as definedfor formula (I) herein.

Amide bond formation (peptide coupling) is conducted under standardpeptide coupling procedures known in the prior art. Optimally, thereaction is conducted in a solvent such as dichloromethane (DCM) at roomtemperature usingbenzotriazol-1-yl-oxytris(dimethylamino)phosphonium-hexafluoorophosphate(BOP) (Castro B et al. Tetrahedron Lett. 1975, 14:1219-1222) and a base,for example N-methyl-morpholine or diisopropylethylamine.

Thionation of the formed amide was performed using Lawesson's reagent(Pons J F et al., Tetrahedron Lett. 2000, 41: 4965-4968).

Cyclisation: the obtained thioamide was then submitted to the conditionsreported by Hitosuyanagi et al. (Hitotsuyanagi Y. et al., J. Org. Chem.2002, 67: 3266-3271) which were slightly modified (5 eq. of hydrazideand 1.1 eq. of mercury (II) acetate in acetonitrile). Cyclisation intotriazoles was generally achieved within three hours. When the hydrazidewas not commercially available, it was prepared by known methods fromits acid or methyl ester precursors.

Deprotection of the tert-butyloxycarbonyl group (Boc) was performed atroom temperature in acidic medium as usually described.

For R5=—CO-alkyl, —CO-cycloalkyl, —CO-cycloalkylalkyl, —CO-aryl,—CO-arylalkyl, —CO-heteroaryl, —CO-heteroarylalkyl, —CO-heterocyclyl,—CO-heterocyclylalkyl, —CO—C*(R9R10)-NH₂, —CO—CH₂—C*(R9R10)-NH₂,—CO—C*(R9R10)-CH₂—NH₂ (R):

For R5=alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl (R):

For R5=alkyl-SO₂—, aryl-SO₂—, arylalkyl-SO₂— (R=alkyl, aryl, arylalkyl):

The compounds of the invention, especially compounds 1 to 190 were namedfrom the drawn formula using the Chem Draw Ultra 8 software(CambridgeSoft Corporation, Cambridge, USA).

The contents of all cited references and patents are hereby incorporatedby reference. The invention is explained in more detail by means of thefollowing examples without, however, being restricted thereto.

EXAMPLES

I) Synthesis of Compounds of the Invention

Example 1(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 1)

Compound 1 was obtained from Boc-(D)-Trp (10 mmoles),(2,4-dimethoxyphenyl)-methanamine, 3-(1H-indol-3-yl)propane hydrazideand Boc-2-amino-2-methylpropanoic acid according to the generalsynthetic schemes with a total yield after purification by HPLC of 35%.

¹H NMR (400 MHz, 300° K, DMSO-d⁶):

δ 1.32 (3H, s, CH₃ Aib), 1.36 (3H, s, CH₃ Aib), 2.93 (2H, m, CH₂—CH₂-indole), 2.97 (2H, m, CH₂—CH₂ -indole), 3.31 (1H, dd, J=14.5,J=6.1, 1H C₂ βTrp), 3.38 (1H, dd, J=14.5, J=9.1, 1H C₂ βTrp), 3.66 (3H,s, o-OCH₃), 3.72 (3H, s, p-OCH₃), 4.93 (1H, d, J=16.9, 1H C₂o,p-dimethoxybenzyl), 5.10 (1H, d, J=16.9, 1H C₂ o,p-dimethoxybenzyl),5.23 (1H, m, CαH Trp), 6.31 (1H, dd, J=8.5, J=1.7, H₅o,p-dimethoxybenzyl), 6.45 (1H, d, J=8.5, H₆ o,p-dimethoxybenzyl), 6.59(1H, d, J=1.7, H₃ o,p-dimethoxybenzyl), 6.88 (1H, t, J=7.5, H₅ Trp),6.94 (1H, t, J=7.5, H₅ indole), 7.04 (1H, t, H₆ Trp), 7.06 (1H, t, H₆indole), 7.08 (1H, s, H₂ indole), 7.11 (1H, s, H₂ Trp), 7.18 (1H, d,J=7.9, H₄ Trp), 7.33 (3H, H₄, H₇ indole, H₇ Trp), 8.05 (2H, s, NH₂ Aib),8.95 (1H, d, J=7.9, NH Trp), 10.80 (1H, s, NH indole), 10.82 (1H, s, NHindole Trp).

¹³C NMR (400 MHz, DMSO-d⁶):

δ 22.4 (CH₂—CH₂ indole), 23.2 (CH₃ Aib), 23.3 (CH₃ Aib), 25.4 (CH₂—CH₂indole), 28.7 (Cβ Trp), 41.3 (CH₂-o,p-dimethoxybenzyl), 45.3 (Cα Trp),55.2 (p-OCH₃), 55.4 (o-OCH₃), 56.3 (Cq Aib), 98.6 (C₃o,p-dimethoxybenzyl), 104.7 (C₅ o,p-dimethoxybenzyl), 109.5 (C₃ Trp),111.3 (C₇ Trp, C₇ indole), 112.9 (C₃ indole), 115.2 (C₁o,p-dimethoxybenzyl), 117.8 (C₄ indole), 117.9 (C₄ Trp), 118.2 (C₅ Trp,C₅ indole), 120.9 (C₆ Trp, C₆ indole), 122.4 (C₂ indole), 124.3 (C₂Trp), 126.8 (C₉ Indole), 126.9 (C₉ Trp), 127.5 (C₆ o,p-dimethoxybenzyl),136.0 (C₈ Trp), 136.2 (C₈ indole), 154.6 (2Cq triazole), 157.3 (C₂o,p-dimethoxybenzyl), 160.4 (C₄ o,p-dimethoxybenzyl), 171.3 (CO Aib).

ESI-MS: found: m/z 606.3 [M+H]⁺/calculated: 604.3 g/mol

Example 2(R)—N-(1-(5-benzyl-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 4)

Compound 4 was obtained from Boc-(D)-Trp (10 mmoles),naphthalen-1-yl-methanamine, 2-phenylacetohydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 42%.

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.18 (3H, s, CH₃ Aib), 1.24 (3H, s, CH₃ Aib), 3.17 (1H, dd, J=14Hz and 5 Hz, CH₂ βTrp), 3.36 (1H, dd, J=14 and 9 Hz, CH₂ βTrp), 4.05(2H, m, CH₂-benzyl), 4.90 (1H, m, CH αTrp), 5.65 (1H, d, J=18 Hz, CH₂-naphtyl), 5.81 (1H, d, J=18 Hz, CH ₂-naphtyl), 6.12 (1H, d, J_(o)=7Hz, H₂ naphtyl), 6.38 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.47 (1H, d, J_(o)=8Hz, H₄ Trp), 6.85 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.03 (1H, d, J_(m)=2 Hz,H₂ Trp), 7.05-7.12 (5H, m, CHar benzyl), 7.15 (1H, d, J_(o)=8 Hz, H₇Trp), 7.19 (1H, d, J_(o)=8 Hz, H₃ naphtyl), 7.58 (2H, m, H₆ and H₇naphtyl), 7.81 (1H, d, J_(o)=8 Hz, H₄ naphtyl), 7.89-8.01 (5H, m, NH₂Aib, H₅ and H₈ naphtyl), 8.92 (1H, d, J=8 Hz, NH amide), 10.73 (1H, s,NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.6 (CH₃ Aib), 29.2 (CH₂ βTrp), 30.5(CH₂-benzyl), 44.0 (CH₂-naphtyl), 45.6 (CH αTrp), 56.6 (Cq Aib), 109.7(C₃ Trp), 111.7 (C₇ Trp), 117.9 (C₄ Trp), 118.4 (C₅ Trp), 121.1 (C₆Trp), 122.1 (C₂ naphtyl), 122.8 (C₈ naphtyl), 124.9 (C₂ Trp), 125.7 (C₃naphtyl), 126.7 (C₆ naphtyl), 126.9 (C₉ Trp), 127.0 (C₇ naphtyl), 128.2(C₄ benzyl), 128.7-129.1 (C₂, C₃, C₅ and C₆ benzyl, C₄ and C₅ naphtyl),129.9 (C₉ naphtyl), 131.5 (C₁ naphtyl), 133.5 (C₁₀ naphtyl), 136.2 (C₁benzyl), 136.4 (C₈ Trp), 154.2 (Cq triazole), 155.7 (Cq triazole), 171.9(CO Aib).

ESI-MS: found: m/z 543.4 [M+H]⁺/calculated: 542.2 g/mol

Example 3(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 5)

Compound 5 was obtained from Boc-(D)-Trp (10 mmoles),naphthalen-1-yl-methanamine, 3-(1H-indol-3-yl)propane hydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 33%.

¹H NMR (400 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.25 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 2.93 (2H, m, CH₂—CH₂-indole), 3.01 (2H, m, CH₂—CH ₂-indole), 3.30 (1H, dd, ³J=14.3 and5.8 Hz, CH₂ βTrp), 3.40 (1H, dd, ³J=14.3 and 8.8 Hz, CH₂ βTrp), 5.03(1H, m, CH αTrp), 5.62 (1H, d, J=18.0 Hz, CH₂-naphtyl), 5.76 (1H, J=18.0Hz, CH₂-naphtyl), 3.36 (1H, d, J_(o)=7.2 Hz, H₂ naphtyl), 6.51 (1H, t,J_(o)=7.4 Hz, H₅ Trp), 6.72 (1H, d, J_(o)=7.9 Hz, H₄ Trp), 6.76 (1H, t,J_(o)=7.5 Hz, H₅ indole), 6.92 (1H, t, J_(o)=7.5 Hz, H₆ Trp), 7.0 (1H,t, J_(o)=7.5 Hz, H₆ indole), 7.02 (1H, d, J=2.0 Hz, H₂ indole), 7.09(1H, d, J=2.0 Hz, H₂ Trp), 7.13 (1H, d, J_(o)=7.9 Hz, H₄ indole), 7.26(1H, J_(o)=7.9 Hz, H₇ Trp), 7.27 (1H, t, J_(o)=8.2 Hz, H₃ naphtyl), 7.29(1H, d, H₇ indole), 7.58-7.64 (2, m, H₆ and H₇ naphtyl), 7.88 (1H, d,J_(o)=8.2 Hz, H₄ naphtyl), 7.93 (1H, d, J_(o)=7.9 Hz, H₈ naphtyl), 7.98(3H, brs, NH₂ Aib), 8.03 (1H, d, J_(o)=8.2 Hz, H₅ naphtyl), 8.96 (1H, d,J_(o)=7.9 Hz, NH Trp), 10.75 (1H, brs, NH indole), 10.77 (1H, brs, NHindole Trp).

¹³C NMR (100 MHz, DMSO-d⁶, 300° K):

δ(ppm) 22.6 (CH₂—CH₂-indole), 23.1 (CH₃ Aib), 23.2 (CH₃ Aib), 25.3(CH₂—CH₂-indole), 28.8 (CH₂ βTrp), 43.3 (CH₂-naphtyl), 45.3 (CH αTrp),56.2 (Cq Aib), 109.4 (C₃ Trp), 111.2 (C₇ indole and C₇ Trp), 112.9 (C₃indole), 117.5 (C₄ Trp), 117.8 (C₄ indole), 118.0 (C₅ Trp), 118.1 (C₅indole), 120.7 (C₆ Trp), 120.8 (C₆ indole), 121.6 (C₂ naphtyl), 122.5(C₂ indole and C₈ naphtyl), 124.4 (C₂ Trp), 125.4 (C₃ naphtyl), 126.3(C₆ naphtyl), 126.6 (C₉ indole, C₉ Trp and C₇ naphtyl), 127.9 (C₄naphtyl), 128.6 (C₅ naphtyl), 129.5 (C₉ naphtyl), 131.4 (C₁ naphtyl),133.1 (C₁₀ naphtyl), 135.9 (C₈ Trp), 136.1 (C₈ indole), 154.7 (2 Cqtriazole), 171.4 (CO Aib).

ESI-MS: found: m/z 596.4 [M+H]⁺/calculated: 595.3 g/mol

Example 4(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 6)

Compound 6 was obtained from Boc-(D)-Trp (10 mmoles),(3-methoxyphenyl)-methanamine, 3-(1H-indol-3-yl)propane hydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 25%.

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.28 (3H, s, CH₃ Aib), 1.30 (3H, s, CH₃ Aib), 2.92 (2H, m, CH₂—CH₂-indole), 2.98 (2H, m, CH₂—CH₂ -indole), 3.33 (1H, dd, J=14.5,J=6.2, 1H C₂ βTrp), 3.40 (1H, dd, J=14.5, J=8.8, 1H C₂ βTrp), 3.66 (3H,s, OCH₃), 5.09 (2H, m, CH₂ m-methoxybenzyl), 5.22 (1H, m, CαH Trp), 6.38(1H, d, J=7.5, H₆ m-methoxybenzyl), 6.59 (1H, s, H₂ m-methoxybenzyl),6.86 (1H, t, H₅ Trp), 6.87 (1H, d, H₄ m-methoxybenzyl), 6.92 (1H, t,J=7.5, H₅ indole), 7.03 (1H, t, J=7.9, H₆ Trp), 7.05 (1H, t, H₆ indole),7.07 (1H, s, H₂ indole), 7.11 (1H, s, H₂ Trp), 7.18 (1H, t, H₅m-methoxybenzyl), 7.19 (1H, d, H₄ Trp), 7.31 (1H, H₄ indole), 7.32 (2H,H₇ Trp, H₇ indole), 8.00 (2H, s, NH₂ Aib), 8.96 (1H, d, J=8.1, NH Trp),10.78 (1H, s, NH indole), 10.80 (1H, s, NH indole Trp).

¹³C NMR (400 MHz, DMSO-d⁶):

δ(ppm) 22.4 (CH₂—CH₂ indole), 23.1 (CH₃ Aib), 23.3 (CH₃ Aib), 25.4(CH₂—CH₂ indole), 28.7 (Cβ Trp), 45.3 (CH₂ m-methoxybenzyl), 45.4 (CαTrp), 55.0 (OCH₃), 56.3 (Cq Aib), 109.5 (C₃ Trp), 111.3 (C₇ Trp, C₇indole), 112.0 (C₂ m-methoxybenzyl), 113.0 (C₄ m-methoxybenzyl, C₃indole), 117.8 (C₄ Trp, C₆ m-methoxybenzyl), 118.0 (C₄ indole), 118.2(C₅ indole), 118.3 (C₅ Trp), 120.8 (C₆ indole), 120.9 (C₆ Trp), 122.4(C₂ indole), 124.3 (C₂ Trp), 126.7 (C₉ indole), 126.9 (C₉ Trp), 130.0(C₅ m-methoxybenzyl), 136.0 (C₈ indole), 136.1 (C₈ Trp), 137.2 (C₁m-methoxybenzyl), 154.3 (2Cq triazole), 159.6 (C₃ m-methoxybenzyl),171.4 (CO Aib).

ESI-MS: found: m/z 576.6 [M+H]⁺/calculated: 575.3 g/mol

Example 5(R)—N-(1-(4-(3-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 7)

Compound 7 was obtained from Boc-(D)-Trp (10 mmoles),(3-methoxyphenyl)-methanamine, 2-phenylacetohydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 30%.

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.25 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 3.24 (1H, dd,J=14.3, J=5.8, 1H CH₂ βTrp), 3.38 (1H, dd, J=14.3, J=9.1, 1H C₂ βTrp),3.61 (3H, s, m-OCH₃), 4.04 (2H, m, CH₂ benzyl), 5.07 (1H, d, J=17.4, 1HC₂ m-methoxybenzyl), 5.13 (1H, d, J=17.4, 1H C₂ m-methoxybenzyl), 5.14(1H, m, CαH Trp), 6.32 (1H, d, J=7.8, H₆ m-methoxybenzyl), 6.40 (1H, m,H₂ m-methoxybenzyl), 6.82 (1H, t, H₅ Trp), 6.83 (1H, d, J=7.8, H₄m-methoxybenzyl), 7.01 (1H, t, J=8.2, H₆ Trp), 7.04 (1H, d, J=8.2, H₄Trp), 7.06 (1H, d, J=2.0, H₂ Trp), 7.12 (2H, m, H₂, H₆ Benzyl), 7.13(1H, t, J=7.9, H₅ m-methoxybenzyl), 7.20 (1H, m, H₄ benzyl), 7.24 (2H,m, H₃, H₅ benzyl), 7.29 (1H, d, J=8.2, H₇ Trp), 7.99 (2H, s, NH₂ Aib),8.92 (1H, d, J=8.2, NH Trp), 10.77 (1H, s, NH indole Trp).

¹³C NMR (400 MHz, DMSO-d⁶):

δ(ppm) 23.0 (CH₃ Aib), 23.3 (CH₃ Aib), 28.6 (C₁ Trp), 30.1 (CH₂ benzyl),45.2 (Cα Trp), 45.6 (CH₂— m-methoxybenzyl), 54.9 (m-OCH₃), 56.2 (CqAib), 109.4 (C₃ Trp), 111.2 (C₇ Trp), 111.7 (C₂ m-methoxybenzyl), 113.1(C₄ m-methoxybenzyl), 117.9 (C₄ Trp, C₆ m-methoxybenzyl), 118.2 (C₅Trp), 120.8 (C₆ Trp), 124.3 (C₂ Trp), 126.6 (C₄ benzyl), 126.8 (C₉ Trp),128.3 (C₃, C₅ benzyl), 128.4 (C₂, C₆ benzyl), 129.9 (C₅m-methoxybenzyl), 135.9 (C₁ benzyl, C₈ Trp), 137.0 (C₁ m-methoxybenzyl),153.5 (Cq triazole), 154.8 (Cq triazole), 159.5 (C₃ m-methoxybenzyl),171.3 (CO Aib).

ESI-MS: found: m/z 523.3 [M+H]⁺/calculated: 522.3 g/mol

Example 6(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 8)

Compound 8 was obtained from Boc-(D)-Trp (10 mmoles), phenylmethanamine,3-(1H-indol-3-yl)propane hydrazide and Boc-2-amino-2-methylpropanoicacid according to the general synthetic schemes with a total yield afterpurification by HPLC of 45%.

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.29 (3H, s, CH₃ Aib), 1.30 (3H, s, CH₃ Aib), 2.88 (2H, m, CH₂—CH₂-indole), 2.97 (2H, m, CH₂—CH₂ -indole), 3.37 (2H, m, CH₂ βTrp),5.11 (2H, s, CH₂ benzyl), 5.21 (1H, m, CαH Trp), 6.86 (1H, t, J=7.4, H₅Trp), 6.88 (2H, H₂, H₆ benzyl), 6.92 (1H, t, J=7.6, H₅ indole), 7.03(1H, t, J=7.6, H₆ Trp), 7.05 (2H, H₆ indole, H₂ indole), 7.09 (1H, d,J=1.8, H₂ Trp), 7.17 (1H, d, J=7.9, H₄ Trp), 7.26 (2H, H₃, H₅ benzyl),7.27 (1H, H₄ benzyl), 7.30 (1H, H₄ indole), 7.32 (2H, H₇ Trp, H₇indole), 8.03 (2H, brs, NH₂ Aib), 8.95 (1H, d, J=8.1, NH Trp), 10.77(1H, s, NH indole), 10.81 (1H, s, NH indole Trp).

¹³C NMR (400 MHz, DMSO-d⁶):

δ(ppm) 22.4 (CH₂—CH₂ indole), 23.1 (CH₃ Aib), 23.3 (CH₃ Aib), 25.4(CH₂—CH₂ indole), 28.7 (Cβ Trp), 45.3 (Cα Trp, CH₂-benzyl), 56.3 (CqAib), 109.5 (C₃ Trp), 111.3 (C₇ Trp, C₇ indole), 113.0 (C₃ indole),117.8 (C₄ Trp), 118.0 (C₄ indole), 118.2 (C₅ indole), 118.3 (C₅ Trp),120.9 (C₆ Trp, C₆ indole), 122.4 (C₂ indole), 124.3 (C₂ Trp), 125.9 (C₂,C₆ benzyl), 126.7 (C₉ Indole), 126.9 (C₉ Trp), 127.6 (C₄ benzyl), 128.8(C₃, C₅ benzyl), 135.7 (C₁ benzyl), 136.0 (C₈ Trp), 136.1 (C₈ indole),154.3 (Cq triazole), 154.5 (Cq triazole), 171.4 (CO Aib).

ESI-MS: found: m/z 546.3 [M+H]⁺/calculated: 545.3 g/mol

Example 7(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 9)

Compound 9 was obtained from Boc-(D)-Trp (10 mmoles), phenylmethanamine,4-(1H-indol-3-yl)butanehydrazide and Boc-2-amino-2-methylpropanoic acidaccording to the general synthetic schemes with a total yield afterpurification by HPLC of 38%.

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.29 (3H, s, CH₃ Aib), 1.31 (3H, s, CH₃ Aib), 1.90 (2H, m,CH₂—CH₂ —CH₂-indole), 2.61 (2H, m, CH₂ —CH₂—CH₂-indole), 2.69 (2H, m,CH₂—CH₂—CH₂ -indole), 3.37 (2H, m, CH₂ βTrp), 5.09 (2H, s, CH₂ benzyl),5.20 (1H, m, CαH Trp), 6.85 (3H, m, H₂, H₆ benzyl, H₅ Trp), 6.94 (1H, t,J=7.5, H₅ indole), 7.01 (1H, s, H₂ indole), 7.02 (1H, t, J=7.8, H₆ Trp),7.05 (1H, t, J=8, H₆ indole), 7.08 (1H, d, J=2.0, H₂ Trp), 7.14 (1H, d,J=8.0, H₄ Trp), 7.25 (3H, m, H₃, H₄, H₅ benzyl), 7.31 (1H, d, J=8.0, H₇Trp), 7.32 (1H, d, J=8.0, H₇ indole), 7.42 (1H, d, J=7.8, H₄ indole),8.03 (2H, s, NH₂ Aib), 8.95 (1H, d, J=8.1, NH Trp), 10.73 (1H, s, NHindole), 10.80 (1H, d, J=2.0, NH indole Trp).

¹³C NMR (400 MHz, DMSO-d⁶):

δ(ppm) 23.1 (CH₃ Aib), 23.3 (CH₃ Aib), 23.8 (CH₂—CH₂—CH₂-indole), 24.1(CH₂—CH₂—CH₂-indole), 27.2 (CH₂—CH₂—CH₂-indole), 28.7 (Cβ Trp), 45.4 (CαTrp), 45.5 (CH₂ benzyl), 56.3 (Cq Aib), 109.4 (C₃ Trp), 111.3 (C₇ Trp,C₇ indole), 113.6 (C₃ indole), 117.8 (C₄ Trp), 118.0 (C₅ indole), 118.2(C₄ indole), 118.3 (C₅ Trp), 120.8 (C₆ indole, C₆ Trp), 122.2 (C₂indole), 124.3 (C₂ Trp), 125.9 (C₂, C₆ benzyl), 126.8 (C₉ Trp), 127.0(C₉ indole), 127.7 (C₄ benzyl), 128.7 (C₃, C₅ benzyl), 135.5 (C₁benzyl), 136.0 (C₈ Trp), 136.2 (C₈ indole), 154.3 (Cq triazole), 154.7(Cq triazole), 171.4 (CO Aib).

ESI-MS: found: m/z 560.4 [M+H]⁺/calculated: 559.3 g/mol

Example 8(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 10)

Compound 10 was obtained from Boc-(D)-Trp (10 mmoles),(3-methoxyphenyl)-methanamine, 4-(1H-indol-3-yl)butanehydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 25%.

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.30 (3H, s, CH₃ Aib), 1.92 (2H, m,CH₂—CH₂ —CH₂-indole), 2.62 (2H, m, CH₂ —CH₂—CH₂-indole), 2.68 (2H, m,CH₂—CH₂—CH₂ -indole), 3.24 (1H, dd, J=14.5, J=5.8, 1H C₂ βTrp), 3.39(1H, dd, J=14.5, J=9.0, 1H C₂ βTrp), 3.66 (3H, s, m-OCH₃), 5.07 (2H, s,CH₂ m-methoxybenzyl), 5.18 (1H, m, CαH Trp), 6.35 (1H, d, J=7.5, H₆m-methoxybenzyl), 6.54 (1H, bs, H₂ m-methoxybenzyl), 6.84 (1H, t, J=7.5,H₅ Trp), 6.87 (1H, dd, J=8.0, J=2.1, H₄ m-methoxybenzyl), 6.94 (1H, t,J=7.3, H₅ indole), 7.02 (1H, t, H₆ Trp), 7.02 (1H, s, H₂ indole), 7.05(1H, t, J=7.8, H₆ indole), 7.08 (1H, d, J=2.1, H₂ Trp), 7.13 (1H, d,J=8.1, H₄ Trp), 7.17 (1H, t, J=8.1, H₅ m-methoxybenzyl), 7.30 (1H, d, H₇Trp), 7.32 (1H, d, J=8, H₇ indole), 7.42 (1H, d, J=7.6, H₄ indole), 7.98(2H, s, NH₂ Aib), 8.93 (1H, d, J=8.2, NH Trp), 10.71 (1H, s, NH indole),10.77 (1H, s, NH indole Trp).

¹³C NMR (400 MHz, DMSO-d⁶):

δ(ppm) 23.1 (CH₃ Aib), 23.3 (CH₃ Aib), 23.9 (CH₂—CH₂—CH₂-indole), 24.3(CH₂—CH₂—CH₂-indole), 27.4 (CH₂—CH₂—CH₂ indole), 28.8 (Cβ Trp), 45.2(CH₂— m-methoxybenzyl), 45.4 (Cα Trp), 55.1 (m-OCH₃), 56.3 (Cq Aib),109.5 (C₃ Trp), 111.3 (C₇ Trp, C₇ indole), 111.8 (C₂ m-methoxybenzyl),113.0 (C₄ m-methoxybenzyl), 113.8 (C₃ indole), 117.8 (C₆m-methoxybenzyl), 117.9 (C₄ Trp), 118.1 (C₅ indole), 118.2 (C₅ Trp, C₄indole), 120.8 (C₆ Trp), 120.9 (C₆ indole), 122.2 (C₂ indole), 124.3 (C₂Trp), 126.8 (C₉ Trp), 127.0 (C₉ Indole), 130.0 (C₅ m-methoxybenzyl),136.0 (C₈ Trp), 136.2 (C₈ indole), 137.4 (C₁ m-methoxybenzyl), 154.3 (Cqtriazole), 154.6 (Cq triazole), 159.7 (C₃ m-methoxybenzyl), 171.4 (COAib).

ESI-MS: found: m/z 590.3 [M+H]⁺/calculated: 589.3 g/mol

Example 9(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 11)

Compound 11 was obtained from Boc-(D)-Trp (10 mmoles),naphthalen-1-ylmethanamine, 4-(1H-indol-3-yl)butanehydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 22%.

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.20 (3H, 5, CH₃ Aib), 1.25 (3H, s, CH₃ Aib), 1.93 (2H, m,CH₂—CH₂—CH ₂-indole), 2.66 (4H, m, CH ₂—CH₂—CH ₂-indole), 3.25 (1H, dd,J=14 Hz and 5 Hz, CH₂ βTrp), 3.40 (1H, dd, J=14 Hz and 9 Hz, CH₂ βTrp),4.95 (1H, m, CH αTrp), 5.66 (1H, d, J=18 Hz, CH₂-naphtyl), 5.81 (1H, d,J=18 Hz, CH₂-naphtyl), 6.37 (1H, d, J_(o)=7 Hz, H₂ naphtyl), 6.43 (1H,t, J_(o)=7 Hz, H₅ Trp), 6.59 (1H, d, J_(o)=8 Hz, H₄ Trp), 6.86 (3H, m,H₅ and H₆ indole, H₆ Trp), 6.95 (1H, d, J=2 Hz, H₂ indole), 7.00 (1H, d,J_(o)=8 Hz, H₄ indole), 7.06 (1H, d, J=2 Hz, H₂ Trp), 7.20-7.33 (4H, m,H₄ and H₇ indole, H₇ Trp, H₃ naphtyl), 7.60 (2H, m, H₆ and H₇ naphtyl),7.87 (1H, d, J_(o)=8 Hz, H₄ naphtyl), 7.99 (5H, m, NH₂ Aib, H₅ and H₈naphtyl), 8.95 (1H, d, J=8 Hz, NH amide), 10.70 (1H, s, NH indole),10.77 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.6 (CH₃ Aib), 24.1 (CH₂—CH₂—CH₂-indole), 24.5(CH₂—CH₂—CH₂-indole), 27.6 (CH₂—CH₂—CH₂-indole), 29.1 (CH₂ βTrp), 44.1(CH₂-naphtyl), 45.7 (CH α Trp), 56.7 (Cq Aib), 109.7 (C₃ Trp), 111.7 (C₇indole and C₇ Trp), 113.9 (C₃ indole), 117.9 (C₄ Trp), 118.5 (C₄ indole,C₅ Trp), 118.6 (C₅ indole), 121.1 (C₆ Trp), 121.2 (C₆ indole), 122.1 (C₂naphtyl), 122.7 (C₂ indole), 122.9 (C₈ naphtyl), 125.0 (C₂ Trp), 125.9(C₃ naphtyl), 126.8 (C₆ naphtyl), 127.0 (C₉ indole), 127.1 (C₇ naphtyl),127.4 (C₉ Trp), 128.5 (C₄ naphtyl), 129.2 (C₅ naphtyl), 129.9 (C₉naphtyl), 131.6 (C₁ naphtyl), 133.6 (C₁₀ naphtyl), 136.4 (C₈ Trp), 136.7(C₈ indole), 155.4 (Cqs triazole), 171.9 (CO Aib).

ESI-MS: found: m/z 610.3 [M+H]⁺/calculated: 609.3 g/mol

Example 10(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 12)

Compound 12 was obtained from Boc-(D)-Trp (10 mmoles),(4-methoxyphenyl)-methanamine, 3-(1H-indol-3-yl)propane hydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 28%.

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.30 (3H, s, CH₃ Aib), 1.33 (3H, s, CH₃ Aib), 2.91 (2H, m, CH₂—CH₂-indole), 2.97 (2H, m, CH₂—CH₂ -indole), 3.37 (2H, d, CH₂ βTrp),3.71(3H, s, OCH₃), 5.02 (2H, s, CH₂ p-methoxybenzyl), 5.23 (1H, m, CαHTrp), 6.78 (4H, m, CHar p-methoxybenzyl), 6.87 (1H, t, J=7.5, H₅ Trp),6.93 (1H, t, J=7.5, H₅ indole), 7.03 (1H, t, H₆ Trp), 7.05 (1H, t, H₆indole), 7.07 (1H, s, H₂ indole), 7.09 (1H, s, H₂ Trp), 7.21 (1H, d,J=8, H₄ Trp), 7.32 (3H, H₄ indole, H₇ Trp, H₇ indole), 8.02 (2H, s, NH₂Aib), 8.97 (1H, d, J=8.1, NH Trp), 10.77 (1H, s, NH indole), 10.80 (1H,s, NH indole Trp).

¹³C NMR (400 MHz,DMSO-d⁶):

δ(ppm) 22.4 (CH₂—CH₂ indole), 23.1 (CH₃ Aib), 23.4 (CH₃ Aib), 25.5(CH₂—CH₂ indole), 28.9 (Cβ Trp), 44.9 (CH₂ p-methoxybenzyl), 45.3 (CαTrp), 55.0 (OCH₃), 56.3 (Cq Aib), 109.5 (C₃ Trp), 111.3 (C₇ Trp, C₇indole), 113.0 (C₃ indole), 114.1 (C₃, C₅ p-methoxybenzyl), 117.9 (C₄Trp), 118.0 (C₄ indole), 118.2 (C₅ indole), 118.3 (C₅ Trp), 120.9 (C₆indole, C₆ Trp), 122.0 (C₂ indole), 124.4 (C₂ Trp), 126.7 (C₉ indole),126.9 (C₉ Trp), 127.3 (C₂, C₆ p-methoxybenzyl), 127.4 (C₁p-methoxybenzyl), 135.9 (C₈ Trp), 136.1 (C₈ indole), 154.2 (Cqtriazole), 154.5 (Cq triazole), 158.4 C₄ p-methoxybenzyl), 171.4 (COAib).

ESI-MS: found: m/z 576.3 [M+H]⁺/calculated: 575.3 g/mol

Example 11(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 13)

Compound 13 was obtained from Boc-(D)-Trp (10 mmoles),(4-methoxyphenyl)-methanamine, 2-phenylacetohydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 37%.

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.24 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 3.26 (1H, dd, ³J=14Hz and 6 Hz, CH₂ βTrp), 3.31 (1H, dd, ³J=14 Hz and 9 Hz, CH₂ βTrp), 3.67(3H, s, OCH₃), 3.99 (2H, s, CH₂-benzyl), 4.99 (2H, s, CH₂-p-methoxybenzyl), 5.12 (1H, m, CH αTrp), 6.67 (4H, m, CHarp-methoxybenzyl), 6.80 (1H, t, J_(o)=8 Hz, H₅ Trp), 6.98 (1H, t, J_(o)=8Hz, H₆ Trp), 7.02-7.06 (4H, m, H₂ and H₆ benzyl, H₂ and H₄ Trp),7.12-7.25 (3H, m, H₃, H₄ and H₅ benzyl), 7.26 (1H, d, J_(o)=8 Hz, H₇Trp), 8.01 (3H, brs, NH₂ Aib), 8.92 (1H, d, J=8 Hz, NH Trp), 10.77 (1H,s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 29.1 (CH₂ βTrp), 30.6 (CH₂-benzyl), 45.7 (CH₂-p-methoxybenzyl), 45.7 (CH αTrp), 55.5 (OCH₃), 56.7(Cq Aib), 109.8 (C₃ Trp), 111.7 (C₇ Trp), 114.5 (C₃ and C₅p-methoxybenzyl), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.8(C₂ Trp), 127.1 (C₂ and C₆ benzyl), 127.3 (C₉ Trp), 127.6 (C₁p-methoxybenzyl), 127.8 (C₂ and C₆ p-methoxybenzyl), 128.8 (C₃, C₄ andC₅ p-methoxybenzyl), 136.3 (C₁ benzyl), 136.4 (C₈ Trp), 153.8 (Cqtriazole), 155.2 (Cq triazole), 159.1 (C₄ p-methoxybenzyl), 171.9 (COAib).

ESI-MS: found: m/z 524.1 [M+H]⁺/calculated: 522.3 g/mol

Example 12(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 15)

Compound 15 was obtained from Boc-(D)-Trp (10 mmoles), hexan-1-amine,3-(1H-indol-3-yl)propane hydrazide and Boc-2-amino-2-methylpropanoicacid according to the general synthetic schemes with a total yield afterpurification by HPLC of 28%.

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 0.77 (3H, t, J=7.2 (CH₂)₅—CH₃ ), 1.01 (4H, m, 2CH₂), 1.11 (2H, m,CH₂ —CH₃), 1.14 (1H, m, 1H N—CH₂—CH₂ ), 1.33 (1H, m, 1H N—CH₂—CH₂ ),1.40 (3H, s, CH₃ Aib), 1.42 (3H, s, CH₃ Aib), 3.05 (2H, m, CH₂—CH₂-indole), 3.10 (2H, m, CH₂—CH₂ -indole), 3.37 (1H, dd, J=14.2,J=7.6, 1H C₂ βTrp), 3.44 (1H, dd, J=14.2, J=7.6, 1H C₂ βTrp), 3.58 (1H,m, 1H N—CH₂), 3.71 (1H, m, 1H N—CH₂), 5.21 (1H, m, CαH Trp), 6.96 (1H,H₅ Trp), 6.97 (1H, H₅ indole), 7.06 (2H, H₆ Trp, H₆ indole), 7.09 (1H,s, H₂ Trp), 7.13 (1H, s, H₂ indole), 7.34 (2H, H₇ Trp, H₇ indole),7.48(1H, d, H₄ indole), 7.50 (1H, H₄ Trp), 8.14 (2H, s, NH₂ Aib), 9.08 (1H,d, J=7.8, NH Trp), 10.84 (1H, s, NH indole), 10.88 (1H, s, NH indoleTrp).

¹³C NMR (400 MHz, DMSO-d⁶):

δ(ppm) 13.7 (CH₂)₅—CH₃ ), 21.7 (CH₂ —CH₃), 22.4 (CH₂—CH_(□) indole),23.1 (CH₃ Aib), 23.3 (CH₃ Aib), 25.1 (CH₂ —CH_(.□)indole), 25.5(CH₃—CH₂—CH₂—CH₂ ), 29.1 (Cβ Trp), 29.3 (N—CH₂—CH₂ ), 30.4 (CH₃—CH₂—CH₂), 42.6 (N—CH₂ —CH₂), 45.6 (Cα Trp), 56.3 (Cq Aib), 109.2 (C₃ Trp),111.4-111.5 (C₇ Trp, C₇ indole), 112.8 (C₃ indole), 117.7 (C₄ Trp),118.0 (C₅ indole), 118.2 (C₄ indole), 118.4 (C₅ Trp), 120.9 (C₆ indole,C₆ Trp), 122.6 (C₂ indole), 124.3 (C₂ Trp), 126.8 (C₉ Trp), 126.9 (C₉indole), 136.0 (C₈ Trp), 136.2 (C₈ indole), 154.0 (Cq triazole), 154.1(Cq triazole), 171.4 (CO Aib). ESI-MS: found: m/z 540.3[M+H]⁺/calculated: 539.3 g/mol

Example 13(S)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 18)

Compound 18 was obtained from Boc-(L)-Trp (10 mmoles),(2,4-dimethoxyphenyl)-methanamine, 3-(1H-indol-3-yl)propane hydrazideand Boc-2-amino-2-methylpropanoic acid according to the generalsynthetic schemes with a total yield after purification by HPLC of 30%.

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.31 (3H, s, CH₃ Aib), 2.89 (2H, m, CH₂CH₂-indole), 2.93 (2H, m, CH₂CH ₂-indole), 3.27 (2H, m, CH₂ βTrp), 3.62(3H, s, o-OCH₃), 3.68 (3H, s, p-OCH₃), 4.89 (1H, d, ³J=17 Hz,CH₂-o,p-dimethoxybenzyl), 5.06 (1H, d, ³J=17 Hz,CH₂-o,p-dimethoxybenzyl), 5.18 (1H, m, CH αTrp), 6.27 (1H, dd, J_(o)=8Hz and J_(p)=2 Hz, H₅ o,p-dimethoxybenzyl), 6.40 (1H, d, 8 Hz, H₆o,p-dimethoxybenzyl), 6.56 (1H, d, J_(p)=2 Hz, H₃ o,p-dimethoxybenzyl),6.83 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.90 (1H, t, J_(o)=7 Hz, H₅ indole),7.02 (1H, t, H₆ Trp), 7.04 (1H, t, H₆ indole), 7.07 (1H s, H₂ indole),7.08 (1H, s, H₂ Trp), 7.12 (1H, d, J_(o)=8 Hz, H₄ Trp), 7.29 (3H, H₄ andH₇ indole, H₇ Trp), 8.00 (3H, brs, NH₂ Aib), 8.93 (1H, d, J=8 Hz, NHamide), 10.76 (1H, s, NH indole), 10.79 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 22.9 (CH₂ CH₂-indole), 23.6 (CH₃ Aib), 23.7 (CH₃ Aib), 25.8(CH₂CH₂-indole), 29.2 (CH₂ βTrp), 41.4 (CH₂-o,p-dimethoxybenzyl), 45.7(CαTrp), 55.7 (p-OCH₃), 55.9 (o-OCH₃), 56.7 (Cq Aib), 99.0 (C₃o,p-dimethoxybenzyl), 105.1 (C₅ o,p-dimethoxybenzyl), 109.9 (C₃ Trp),111.8 (C₇ Trp, C₇ indole), 113.4 (C₃ indole), 115.6 (C₁o,p-dimethoxybenzyl), 118.3 (C₄ indole), 118.4 (C₄ Trp), 118.6 (C₅ Trp,C₅ indole), 121.3 (C₆ Trp, C₆ indole), 122.6 (C₂ indole), 124.4 (C₂Trp), 127.2 (C₉ indole), 127.3 (C₉ Trp), 128.0 (C₆ o,p-dimethoxybenzyl),136.4 (C₈ Trp), 136.6 (C₈ indole), 155.0 (2 Cq triazole), 157.7 (C₂o,p-dimethoxybenzyl), 160.9 (C₄ o,p-dimethoxybenzyl), 171.6 (CO Aib).

ESI-MS: found: m/z 606.2 [M+H]⁺/calculated: 605.3 g/mol

Example 14(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 23)

Compound 23 was obtained from Boc-(D)-Trp (10 mmoles),(4-methoxyphenyl)-methanamine, 4-(1H-indol-3-yl)butanehydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 25%.

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.30 (3H, s, CH₃ Aib), 1.84 (2H, m, CH₂CH₂CH₂-indole), 2.58 (2H, m, CH ₂CH₂CH₂-indole), 2.65 (2H, m, CH₂CH₂CH₂-indole), 3.34 (2H, d, ³J=7 Hz, CH₂ βTrp), 3.67 (3H, s, OCH₃), 4.96(2H, s, CH₂-p-methoxybenzyl), 5.19 (1H, m, CH αTrp), 6.71 (4H, s, CH arp-methoxybenzyl), 6.89 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.92 (1H, t, J_(o)=7Hz, H₅ indole), 7.02 (1H, s, H₂ indole), 7.05 (1H, s, H₂ Trp), 7.14 (1H,d, J_(o)=8 Hz, H₄ Trp), 7.33 (3H, H₄ indole, H₇ Trp, H₇ indole), 8.02(3H, brs, NH₂ Aib), 7.90 (1H, d, J=8 Hz, NH amide), 10.73 (1H, s, NHindole), 10.79 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 24.3 (CH₂CH₂ CH₂-indole), 24.8(CH₂ CH₂CH₂-indole), 27.7 (CH₂CH₂CH₂-indole), 29.1 (Cβ Trp), 45.5(N—CH₂-p-methoxybenzyl), 45.8 (CαTrp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.8(C₃ Trp), 111.7 (C₇ Trp, C₇ indole), 114.0 (C₃ indole), 114.5 (C₃, C₅p-methoxybenzyl), 118.3 (C₄ indole, C₄ Trp), 118.5 (C₅ indole), 118.8(C₅ Trp), 121.3 (C₆ indole, C₆ Trp), 127.3 (C₉ indole), 127.4 (C₉ Trp),127.6 (C₁ p-methoxybenzyl), 127.9 (C₂, C₆ p-methoxybenzyl, C₂ Trp, C₂indole), 136.1 (C₈ indole), 136.4 (C₈ Trp), 154.7 (Cq triazole), 155.1(Cq triazole), 159.2 (C₄ p-methoxybenzyl), 171.9 (CO Aib).

ESI-MS: found: m/z 590.0 [M+H]⁺/calculated: 589.3 g/mol

Example 15(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2-methoxy)benzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 25)

Compound 25 was obtained from Boc-(D)-Trp (10 mmoles),(2-methoxyphenyl)-methanamine, 3-(1H-indol-3-yl)propane hydrazide andBoc-2-amino-2-methylpropanoic acid according to the general syntheticschemes with a total yield after purification by HPLC of 28%.

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 2.90 (2H, m, CH₂—CH₂-indole), 2.96 (2H, m, CH₂—CH ₂-indole), 3.29 (2H, m, CH₂ βTrp),3.65 (3H, s, OCH₃), 5.09 (3H, m, CH ₂-o-methoxybenzyl and CH αTrp), 6.49(1H, d, J_(o)=8 Hz, H₃ o-methoxybenzyl), 6.76 (1H, t, J_(o)=8 Hz, H₅Trp), 6.81 (1H, t, J_(o)=8 Hz, H₅ indole), 6.89 (1H, t, J_(o)=7 Hz, H₆Trp), 6.96 (1H, t, J_(o)=8 Hz, H₆ indole), 6.98 (1H, s, H₂ indole), 7.02(3H, m, H₄, H₅ and H₆ o-methoxybenzyl), 7.07 (1H, d, J_(o)=6 Hz, H₄Trp), 7.18 (1H, m, H₄ indole), 7.29 (2H, m, H₇ indole and H₇ Trp), 8.07(3H, brs, NH₂ Aib), 8.97 (1H, d, J=8 Hz, NH amide), 10.80 (1H, s, NHindole), 10.82 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 22.8 (CH₂—CH₂-indole), 23.6 (CH₃ Aib), 23.7 (CH₃ Aib), 25.8(CH₂—CH₂-indole), 29.1 (CH₂ βTrp), 42.3 (CH₂-o-methoxybenzyl), 45.7 (CHα Trp), 55.8 (OCH₃), 56.7 (Cq Aib), 109.8 (C₃ Trp), 111.5 (C₃o-methoxybenzyl), 111.8 (C₇ indole and C₇ Trp), 113.2 (C₃ indole), 118.2(C₄ Trp), 118.4 (C₄ indole), 118.7 (C₅ indole and C₅ Trp), 121.0 (C₆indole), 121.3 (C₆ Trp), 121.4 (C₅ o-methoxybenzyl), 123.0 (C₂ indoleand C₂ Trp), 123.3 (C₁ o-methoxybenzyl), 127.0 (C₄ o-methoxybenzyl),127.1 (C₉ indole), 127.3 (C₉ Trp), 129.8 (C₆ o-methoxybenzyl), 136.4 (C₈indole), 136.6 (C₈ Trp), 155.2 (Cq triazole), 171.9 (CO Aib).

ESI-MS: found: m/z 576.1 [M+H]⁺/calculated: 575.3 g/mol

Data on further exemplary embodiments that were synthesized according tothe general sysnthesis schemes are compiled below (please refer also toTable 1):

(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 3)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.32 (s, 3H, CH₃ Aib), 1.37 (s, 3H, CH₃ Aib), 1.86 (2H, m, CH₂—CH₂—CH₂-indole), 2.38 (2H, m, CH ₂—CH₂—CH₂-indole), 2.65 (4H, m,CH₂—CH₂—CH ₂-indole and CH₂—CH ₂-phenyl), 3.38 (2H, m, CH ₂—CH₂-phenyl),3.74 (1H, m, CH₂ βTrp), 3.92 (1H, m, CH₂ βTrp), 5.23 (1H, m, CH αTrp),6.78 (2H, m, H₅ indole and H₅ Trp), 6.93 (1H, t, J_(o)=8 Hz, H₆ Trp),7.01 (3H, m, H₆ indole, H₂ and H₆ phenyl), 7.05 (1H, d, J=2 Hz, H₂ Trp),7.08 (1H, d, J=2 Hz, H₂ indole), 7.15 (3H, m, H₃, H₄ and H₅ phenyl),7.29 (1H, d, J_(o)=8 Hz, H₄ Trp), 7.31 (1H, d, Jo=8 Hz, H₇ Trp), 7.44(1H, d, J_(o)=8 Hz, H₇ indole), 7.46 (1H, d, J_(o)=8 Hz, H₄ indole),8.06 (3H, brs, NH₂ Aib), 9.05 (1H, d, 8 Hz, NH amide), 10.76 (1H, s, NHindole), 10.85 (1H, d, J=2 Hz, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.6 (CH₂—CH₂—CH₂-indole), 23.9 (CH₃ Aib), 24.5(CH₂—CH₂—CH₂-indole), 27.3 (CH₂—CH₂—CH₂-indole), 29.4 (CH₂ βTrp), 35.7(CH₂—CH₂-phenyl), 44.5 (CH₂—CH₂-phenyl), 46.1 (CH αTrp), 56.8 (Cq Aib),109.6 (C₃ Trp), 111.8 (C₇ indole), 111.9 (C₇ indole), 113.9 (C₃ indole),118.3 (C₄ Trp), 118.6 (C₅ indole), 118.7 (C₄ indole), 118.9 (C₅ Trp),121.3 (C₆ Trp), 121.4 (C₆ indole), 122.8 (C₂ indole and C₂ Trp), 127.1(C₄ phenyl), 127.3 (C₉ Trp), 127.5 (C₉ indole), 128.8 (C₂ and C₆phenyl), 129.1 (C₃ and C₅ phenyl), 136.5 (C₁ phenyl), 136.8 (C₈ Trp),137.2 (C₈ indole), 154.7 (Cq triazole), 172.0 (CO Aib).

(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 16)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 0.74 (3H, t, J=6 Hz, CH ₃—CH₂—CH₂—CH₂—CH₂—CH₂), 0.95 (4H, brs,CH₃—CH₂—CH ₂—CH ₂—CH₂—CH₂), 1.06 (3H, m, CH₃—CH ₂—CH₂—CH₂—CH₂—CH₂ and 1HN—CH₂—CH ₂), 1.38 (7H, s, CH₃ Aib and 1H N—CH₂—CH ₂), 1.97 (2H, m,CH₂—CH ₂—CH₂-indole), 2.71 (4H, m, CH ₂—CH₂—CH ₂-indole), 3.37 (2H, m,CH₂ βTrp), 3.56 (2H, m, N—CH ₂), 5.15 (1H, m, CH αTrp), 6.91 (2H, m, H₅indole and H₅ Trp), 7.00 (2H, m, H₆ indole and H₆ Trp), 7.07 (2H, s, H₂indole and H₂ Trp), 7.29 (2H, d, J_(o)=8 Hz, H₇ indole and H₇ Trp), 7.45(2H, d, J_(o)=7 Hz, H₄ indole and H₄ Trp), 8.15 (3H, brs, NH₂ Aib), 9.10(1H, d, J=6 Hz, NH amide), 10.77 (1H, s, NH indole), 10.85 (1H, s, NHindole Trp).

¹³C NMR (75 MHz, DMSO-D⁶, 300° K):

δ(ppm) 14.2 (CH₃—CH₂—CH₂—CH₂—CH₂—CH₂), 22.2 (CH₃—CH₂—CH₂—CH₂—CH₂—CH₂ andCH₂—CH₂—CH₂-indole), 23.6 (CH₃ Aib), 23.7 (CH₃ Aib), 24.5(CH₂—CH₂—CH₂-indole), 25.9 (CH₃—CH₂—CH₂—CH₂—CH₂—CH₂), 27.5 (CH₂ βTrp andCH₂—CH₂—CH₂-indole), 29.7 (N—CH₂—CH₂), 30.8 (CH₃—CH₂—CH₂—CH₂—CH₂—CH₂),43.2 (N—CH₂), 46.1 (CH αTrp), 56.8 (Cq Aib), 109.5 (C₃ Trp), 111.8 (C₇Trp), 111.9 (C₇ indole), 113.9 (C₃ indole), 118.1 (C₄ Trp), 118.5 (C₅indole), 118.6 (C₄ indole), 118.9 (C₅ Trp), 121.3 (C₆ indole and C₆Trp), 122.8 (C₂ indole and C₂ Trp), 127.3 (C₉ Trp), 127.4 (C₉ indole),136.5 (C₈ Trp), 136.8 (C₈ indole), 154.7 (Cq triazole), 172.0 (CO Aib).

(R)—N-(1-(4,5-bis(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 17)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.30 (3H, s, CH₃ Aib), 1.37 (3H, s, CH₃ Aib), 2.50 (2H, m,N—CH₂—CH ₂-indole), 2.68 (2H, t, J_(o)=8 Hz, C—CH₂—CH ₂-indole), 2.91(2H, t, J_(o)=8 Hz, C—CH₂—CH ₂-indole), 3.34 (2H, m, N—CH ₂—CH₂-indole),3.93 (2H, m, CH₂ βTrp), 5.25 (1H, m, CH αTrp), 6.72-6.94 (4H, m, H₅ andH₆ Trp, H₅ indole from C—CH₂—CH₂-indole and H₅ indole fromN—CH₂—CH₂-indole), 6.98-7.04 (4H, m, H₂ Trp, H₆ indole fromC—CH₂—CH₂-indole, H₂ and H₆ indole from N—CH₂—CH₂-indole), 7.11 (1H, s,H₂ indole from C—CH₂—CH₂-indole), 7.19 (1H, d, J_(o)=8 Hz, H₄ indolefrom N—CH₂—CH₂-indole), 7.28 (3H, m, H₄ and H₇ Trp, H₇ indole fromN—CH₂—CH₂-indole), 7.40 (1H, d, J_(o)=8 Hz, H₇ indole fromC—CH₂—CH₂-indole), 7.44 (1H, d, J_(o)=8 Hz, H₄ indole fromC—CH₂—CH₂-indole), 8.04 (3H, brs, NH₂ Aib), 9.69 (1H, d, J=8 Hz, NHamide), 10.73 (1H, s, NH indole from C—CH₂—CH₂-indole), 10.82 (1H, d,J=2 Hz, NH indole Trp), 10.84 (1H, s, NH indole from N—CH₂—CH₂-indole).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 22.7 (C—CH₂—CH₂-indole), 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 25.4(C—CH₂—CH₂-indole), 26.0 (N—CH₂—CH₂-indole), 29.6 (CH₂ βTrp), 43.9(N—CH₂—CH₂-indole), 46.0 (CH αTrp), 56.8 (Cq Aib), 109.5 (C₃ indole fromN—CH₂—CH₂-indole), 109.9 (C₃ Trp), 111.7 (C₇ Trp), 111.9 (C₇ indole fromN—CH₂—CH₂-indole and C₇ indole from C—CH₂—CH₂-indole), 113.5 (C₃ indolefrom C—CH₂—CH₂-indole), 118.3 (C₄ indole from N—CH₂—CH₂-indole), 118.4(C₄ Trp), 118.5 (C₅ indole from C—CH₂—CH₂-indole), 118.7 (C₄ indole fromC—CH₂—CH₂-indole), 118.9 (C₅ Trp), 119.0 (C₅ indole fromN—CH₂—CH₂-indole), 121.3 (C₆ Trp), 121.5 (C₆ indole fromC—CH₂—CH₂-indole and C₆ indole from N—CH₂—CH₂-indole), 122.8 (C₂ Trp, C₂indole from C—CH₂—CH₂-indole and indole from N—CH₂—CH₂-indole), 127.1(C₉ Trp), 127.2 (C₉ indole from C—CH₂—CH₂-indole), 127.4 (C₉ indole fromN—CH₂—CH₂-indole), 136.5 (C₈ Trp and C₈ indole from C—CH₂—CH₂-indole),136.6 (C₈ indole from N—CH₂—CH₂-indole), 154.5 (Cq triazole), 154.8 (Cqtriazole), 171.8 (CO amide).

(R)—N-(1-(4-(3-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 19)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.24 (3H, s, CH₃ Aib), 1.27 (3H, s, CH₃ Aib), 2.82 (4H, m, CH₂—CH ₂-phenyl), 3.32 (2H, m, CH₂βTrp), 3.63 (3H, s, OCH₃), 5.08 (2H, m,CH ₂-m-methoxybenzyl), 5.18 (1H, m, CH αTrp), 6.35 (1H, d, J_(o)=8 Hz,H₆ m-methoxybenzyl), 6.57 (1H, s, H₂ m-methoxybenzyl), 6.82 (1H, t,J_(o)=8 Hz, H₅ Trp), 6.84 (1H, d, J_(o)=8 Hz, H₄ m-methoxybenzyl), 6.99(1H, t, J_(o)=8 Hz, H₆ Trp), 7.08 (1H, m, H₄ phenyl), 7.11-7.16 (5H, m,H₂ and H₄ Trp, H₂ and H₆ phenyl, H₅ m-methoxybenzyl), 7.20 (2H, m, H₃and H₅ phenyl), 7.27 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂Aib), 8.96 (1H, d, J=8 Hz, NH amide), 10.81 (1H, d, J=2 Hz, NH indole).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.4 (CH₂—CH₂-phenyl), 29.1 (CH₂βTrp), 32.7 (CH₂—CH₂-phenyl), 45.7 (CH αTrp), 45.8(CH₂-m-methoxybenzyl), 55.5 (OCH₃), 56.7 (Cq Aib), 109.8 (C₃ Trp), 111.8(C₇ Trp), 112.5 (C₂ m-methoxybenzyl), 113.5 (C₄ m-methoxybenzyl), 118.2(C₄ Trp), 118.4 (C₆ m-methoxybenzyl), 118.7 (C₅ Trp), 121.3 (C₆ Trp),124.8 (C₂ Trp), 126.5 (C₄ phenyl), 127.3 (C₉ Trp), 128.7 (C₂, C₃, C₅ andC₆ phenyl), 130.5 (C₅ m-methoxybenzyl), 136.4 (C₈ Trp), 137.7 (C₁m-methoxybenzyl), 170.9 (C₁ phenyl), 154.6 (Cq triazole), 154.9 (Cqtriazole), 160.1 (C₃ m-methoxybenzyl), 171.9 (CO amide).

(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 20)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.28 (3H, s, CH₃ Aib), 1.32 (3H, s, CH₃ Aib), 2.46 (2H, m,CH₂—CH₂-phenyl), 2.82 (2H, m, CH₂—CH ₂-phenyl), 3.35 (2H, d, J=7 Hz, CH₂βTrp), 3.68 (3H, s, OCH₃), 5.02 (2H, s, CH ₂-p-methoxybenzyl), 5.22 (1H,m, CH αTrp), 6.73-6.81 (4H, m, CHar p-methoxybenzyl), 6.84 (1H, t,J_(o)=7 Hz, H₅ Trp), 7.00 (1H, t, J_(o)=7 Hz, H₆ Trp), 7.05-7.11 (4H, m,H₂ and H₆ phenyl, H₂ and H₄ Trp), 7.14-7.22 (3H, m, H₃, H₄ and H₅phenyl), 7.29 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.09 (3H, brs, NH₂ Aib), 8.99(1H, d, J=8 Hz, NH amide), 10.83 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.5 (CH₂—CH₂-phenyl), 29.1 (CH₂βTrp), 32.6 (CH₂—CH₂-phenyl), 45.5 (CH₂-p-methoxybenzyl), 45.7 (CHαTrp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 114.6(C₃ and C₅ p-methoxybenzyl), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆Trp), 124.9 (C₂ Trp), 126.6 (C₂ and C₆ phenyl), 127.3 (C₉ Trp), 127.6(C₁ p-methoxybenzyl), 128.0 (C₂ and C₆ p-methoxybenzyl), 128.7 (C₃, C₄and C₅ phenyl), 136.4 (C₈ Trp), 140.8 (C₁ phenyl), 154.5 (Cq triazole),154.8 (Cq triazole), 159.2 (C₄ p-methoxybenzyl), 172.0 (CO Aib).

(R)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 22)

¹H NMR (300 MHz, DMSO-d⁶, 300°K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.31 (3H, s, CH₃ Aib), 1.73 (2H, m,CH₂—CH₂—CH₂-phenyl), 2.47 (2H, m, CH ₂—CH₂—CH₂-phenyl), 2.52 (2H, t,³J=7 Hz, CH₂—CH₂—CH ₂-phenyl), 3.35 (2H, d, J=7 Hz, CH₂ βTrp), 3.68 (3H,s, OCH₃), 4.98 (2H, s, CH₂-p-methoxybenzyl), 5.20 (1H, m, CH αTrp), 6.75(4H, m, CHar p-methoxybenzyl), 6.82 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.99(1H, t, J_(o)=7 Hz, H₆ Trp), 7.04-7.07 (4H, m, H₂ and H₆ phenyl, H₂ andH₄ Trp), 7.13-7.24 (3H, m, H₃, H₄ and H₅ phenyl), 7.29 (1H, d, J_(o)=8Hz, H₇ Trp), 8.03 (3H, brs, NH₂ Aib), 8.96 (1H, d, J=8 Hz, NH amide),10.80 (1H, d, J=2 Hz, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.6 (CH₃ Aib), 24.06 (CH₂—CH₂—CH₂-phenyl), 28.5(CH₂—CH₂—CH₂-phenyl),29.2 (CH₂ βTrp), 34.7 (CH₂—CH₂—CH₂-phenyl), 45.5(CH₂-p-methoxybenzyl), 45.8 (CH αTrp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.8(C₃ Trp), 111.8 (C₇ Trp), 114.6 (C₃ and C₅ p-methoxybenzyl), 118.3 (C₄Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.2 (C₂ and C₆phenyl), 127.3 (C₉ Trp), 127.8 (C₁ p-methoxybenzyl), 127.9 (C₂ and C₆p-methoxybenzyl), 128.7 (C₃, C₄ and C₅ phenyl), 136.4 (C₈ Trp), 141.7(C₁ phenyl), 154.8 (Cq triazole), 159.2 (C₄ p-methoxybenzyl), 171.9 (COAib).

(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-(3-(1H-indol-3-yl)propyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 24)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.29 (3H, s, CH₃ Aib), 1.35 (3H, s, CH₃ Aib), 1.78 (2H, m, CH₂—CH₂—CH₂-indole), 2.34 (2H, m, CH ₂—CH₂—CH₂-indole), 2.48 (2H, m, N—CH₂—CH₂-indole), 2.80 (2H, m, CH₂—CH₂—CH ₂-indole), 3.34 (2H, m, N—CH₂—CH₂-indole), 3.94 (2H, m, CH₂ βTrp), 5.27 (1H, m, CH αTrp), 6.73-6.94(4H, m, H₅ and H₆ Trp, H₅ indole from N—CH₂—CH₂-indole and H₅ indolefrom CH₂—CH₂—CH₂-indole), 6.99-7.04 (5H, m, H₂ Trp, H₂ and H₆ indolefrom N—CH₂—CH₂-indole, H₂ and H₆ indole from CH₂—CH₂—CH₂-indole), 7.20(1H, d, J_(o)=8 Hz, H₄ indole from N—CH₂—CH₂-indole), 7.29 (3H, m, H₄and H₇ Trp, H₇ indole from N—CH₂—CH₂-indole), 7.40 (1H, d, J_(o)=8 Hz,H₇ indole from CH₂—CH₂—CH₂-indole), 7.44 (1H, d, J_(o)=8 Hz, H₄ indolefrom CH₂—CH₂—CH₂-indole), 8.05 (3H, brs, NH₂ Aib), 9.07 (1H, d, J=8 Hz,NH amide), 10.75 (1H, s, NH indole from CH₂—CH₂—CH₂-indole), 10.86 (1H,s, NH indole Trp), 10.90 (1H, s, NH indole from N—CH₂—CH₂-indole).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 24.5 (CH₂—CH₂—CH₂-indole), 25.8(CH₂—CH₂—CH₂-indole), 27.2 (CH₂—CH₂—CH₂-indole), 29.4 (CH₂ βTrp), 44.1(N—CH₂—CH₂-indole), 46.0 (CH αTrp), 52.9 (N—CH₂—CH₂-indole), 56.8 (CqAib), 109.7 (C₃ Trp and C₃ indole from N—CH₂—CH₂-indole), 111.8 (C₇Trp), 111.9 (C₇ indole from N—CH₂—CH₂-indole and C₇ indole fromCH₂—CH₂—CH₂-indole), 114.0 (C₃ indole from CH₂—CH₂—CH₂-indole), 118.2(C₄ indole from N—CH₂—CH₂-indole), 118.3 (C₄ Trp), 118.5 (C₅ indole fromCH₂—CH₂—CH₂-indole), 118.6 (C₄ indole from CH₂—CH₂—CH₂-indole), 118.9(C₅ Trp), 119.0 (C₅ indole from N—CH₂—CH₂-indole), 121.3 (C₆ Trp), 121.4(C₆ indole from CH₂—CH₂—CH₂-indole), 121.6 (C₆ indole fromN—CH₂—CH₂-indole), 122.7 (C₂ Trp, C₂ indole from N—CH₂—CH₂-indole and C₂indole from CH₂—CH₂—CH₂-indole), 127.1 (C₉ Trp), 127.4 (C₉ indole fromN—CH₂—CH₂-indole and C₉ indole from CH₂—CH₂—CH₂-indole), 136.4 (C₈ Trp),136.5 (C₈ indole from CH₂—CH₂—CH₂-indole), 136.7 (C₈ indole fromN—CH₂—CH₂-indole), 154.7 (2 Cq triazole), 171.9 (CO amide).

(R)—N-(1-(4-(2-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 26)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.26 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 2.78-2.92 (4H, m,CH ₂—CH ₂-phenyl), 3.29 (2H, m, CH₂ βTrp), 3.65 (3H, s, OCH₃), 4.97-5.21(3H, m, CH αTrp and CH₂-o-methoxybenzyl), 6.52 (1H, d, J_(o)=7 Hz, H₃o-methoxybenzyl), 6.78 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.82 (1H, t, J_(o)=8Hz, H₆ Trp), 6.84-7.04 (3H, m, H₄, H₅ and H₆ o-methoxybenzyl), 7.15 (1H,d, J_(o)=7 Hz, H₄ Trp), 7.19-7.29 (4H, m, H₃, H₄ and H₅ phenyl, H₇ Trp),8.03 (3H, brs, NH₂ Aib), 8.94 (1H, d, J=8 Hz, NH amide), 10.82 (1H, s,NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.7 (CH₃ Aib), 26.3 (CH₂—CH₂-phenyl), 29.0 (CH₂βTrp), 32.5 (CH₂—CH₂-phenyl), 42.3 (CH₂-o-methoxybenzyl), 45.7 (CHαTrp), 55.8 (OCH₃), 56.7 (Cq Aib), 109.7 (C₃ Trp), 111.5 (C₇ Trp), 111.8(C₃ o-methoxybenzyl), 118.2 (C₄ Trp), 118.7 (C₅ Trp), 121.0 (C₆ Trp),121.3 (C₅ o-methoxybenzyl), 123.2 (C₁ o-methoxybenzyl), 124.9 (C₂ Trp),126.6 (C₂ and C₆ phenyl), 127.2 (C₉ Trp and C₄ o-methoxybenzyl), 128.7(C₃, C₄ and C₅ phenyl), 129.9 (C₆ o-methoxybenzyl), 136.4 (C₈ Trp),140.6 (C₁ phenyl), 154.8 (Cq triazole), 155.2 (Cq triazole), 156.7 (C₂o-methoxybenzyl), 171.9 (CO Aib).

(R)—N-(2-(1H-indol-3-yl)-1-(4-(naphthalen-1-ylmethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 27)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.21 (3H, s, CH₃ Aib), 1.25 (3H, s, CH₃ Aib), 2.46 (2H, m, CH₂—CH₂-phenyl), 2.88 (2H, m, CH₂—CH ₂-phenyl), 3.26 (2H, dd, ³J=14 Hz and6 Hz, CH₂ βTrp), 3.36 (2H, dd, ³J=14 Hz and 9 Hz, CH₂ βTrp), 4.99 (1H,m, CH αTrp), 5.65 (1H, d, ³J=18 Hz, CH ₂-naphtyl), 5.78 (1H, d, ³J=18Hz, CH₂ -naphtyl), 6.29 (1H, d, J_(o)=7 Hz, H₂ naphtyl), 6.45 (1H, t,J_(o)=7 Hz, H₅ Trp), 6.62 (1H, d, J_(o)=8 Hz, H₄ Trp), 6.88 (1H, t,J_(o)=8 Hz, H₆ Trp), 7.04-7.06 (4H, m, H₂ and H₇ Trp, H₂ and H₆ phenyl),7.07-7.25 (H₃ naphtyl, H₃, H₄ and H₅ phenyl), 7.57-7.60 (2H, m, H₆ andH₇ naphtyl), 7.86 (1H, d, J_(o)=8 Hz, H₄ naphtyl), 7.98-8.00 (4H, m, H₅and H₈ naphtyl, NH₂ Aib), 8.96 (1H, d, J=8 Hz, NH amide), 10.77 (1H, s,NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.6 (CH₃ Aib), 26.3 (CH₂CH₂-phenyl), 29.2 (CH₂βTrp), 32.6 (CH₂—CH₂-phenyl), 43.8 (CH₂-naphtyl), 45.6 (CH αTrp), 56.7(Cq Aib), 109.7 (C₃ Trp), 111.7 (C₇ Trp), 117.9 (C₄ Trp), 118.4 (C₅Trp), 121.1 (C₆ Trp), 122.1 (C₂ naphtyl), 123.0 (C₈ naphtyl), 124.9 (C₂Trp), 125.9 (C₃ naphtyl), 126.5 (C₆ naphtyl), 126.9 (C₂ and C₆ phenyl),127.0 (C₉ Trp and C₇ naphtyl), 127.1 (C₄ naphtyl), 128.4 (C₅ naphtyl),128.7 (C₃, C₄ and C₅ phenyl), 130.0 (C₉ naphtyl), 131.7 (C₁ naphtyl),133.6 (C₁₀ naphtyl), 136.4 (C₈ Trp), 140.8 (C₁ phenyl), 154.8 (Cqtriazole), 155.3 (Cq triazole), 171.9 (CO Aib).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,4-dichlorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 28)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.26 (6H, s, CH₃ Aib), 2.87 (2H, m, CH ₂—CH₂-indole), 2.96 (2H,m, CH₂—CH ₂-indole), 3.32 (2H, m, CH₂ βTrp), 5.13 (3H, m, CH αTrp andCH₂-m,p-dichlorobenzyl), 6.58 (1H, d, J_(o)=8 Hz, H₆m,p-dichlorobenzyl), 6.85 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.96 (1H, t,J_(o)=7 Hz, H₅ indole), 7.01 (2H, m, H₆ indole and H₆ Trp), 7.04 (1H, s,H₂ Trp), 7.08 (1H, s, H₂ indole), 7.13 (1H, d, J_(o)=8 Hz, H₅m,p-dichlorobenzyl), 7.20-7.30 (4H, m, H₄ and H₇ indole, H₇ Trp and H₂m,p-dichlorobenzyl), 7.36 (1H, d, J_(o)=8 Hz, H₄ Trp), 8.08 (3H, brs,NH₂ Aib), 8.98 (1H, d, J=8 Hz, NH amide), 10.80 (1H, s, NH indole),10.82 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 22.8 (CH₂—CH₂-indole), 23.4 (CH₃ Aib), 23.8 (CH₃ Aib), 25.8(CH₂—CH₂-indole), 29.0 (CH₂ βTrp), 44.8 (CH₂-m,p-dichlorobenzyl), 45.6(CH αTrp), 56.8 (Cq Aib), 109.7 (C₃ indole), 111.8 (C₇ indole and C₇Trp), 118.1 (C₄ Trp), 118.4 (C₅ indole), 118.6 (C₄ indole and C₅ Trp),121.3 (C₆ indole and C₆ Trp), 123.0 (C₂ indole and C₂ Trp), 126.4 (C₆m,p-dichlorobenzyl), 127.1 (C₉ Trp), 127.3 (C₉ indole), 128.6 (C₂m,p-dichlorobenzyl), 130.9 (C₄ m,p-dichlorobenzyl), 131.3 (C₅m,p-dichlorobenzyl), 132.0 (C₃ m,p-dichlorobenzyl), 136.4 (C₈ Trp),136.6 (C₈ indole), 137.2 (C₁ m,p-dichlorobenzyl), 154.7 (Cq triazole),155.1 (Cq triazole), 172.0 (CO Aib).

(R)—N-(1-(4-(4-fluorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 30)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 3.33 (2H, m, CH₂βTrp), 4.02 (2H, s, CH₂-benzyl), 5.10 (3H, m, CH₂-p-fluorobenzyl and CHαTrp), 6.71 (2H, m, H₃ and H₅ p-fluorobenzyl), 6.80 (1H, t, J_(o)=8 Hz,H₅ Trp), 6.90 (2H, d, J_(o)=8 Hz, H₂ and H₆ p-fluorobenzyl), 6.94 (1H,t, J_(o)=8 Hz, H₆ Trp), 6.99-7.10 (4H, m, H₂ and H₄ Trp, H₂ and H₆benzyl), 7.20 (3H, m, H₃, H₄ and H₅ benzyl), 7.27 (1H, d, J_(o)=8 Hz, H₇Trp), 8.09 (3H, brs, NH₂ Aib), 8.97 (1H, d, J=8 Hz, NH amide), 10.79(1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 29.0 (CH₂ βTrp), 31.1(CH₂-benzyl), 45.7 (CH₂-p-fluorobenzyl), 45.8 (CH αTrp), 56.8 (Cq Aib),109.6 (C₃ Trp), 111.8 (C₇ Trp), 115.6 and 115.9 (C₃ and C₅p-fluorobenzyl), 118.2 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.8(C₂ Trp), 127.1 (C₄ benzyl), 127.2 (C₉ Trp), 128.8 and 128.9 (C₂ and C₆p-fluorobenzyl), 129.4 (C₂, C₃, C₅ and C₆ p-fluorobenzyl), 131.6 (C₁p-fluorobenzyl), 135.9 (C₁ benzyl), 136.4 (C₈ Trp), 154.0 (C₄p-fluorobenzyl), 155.3 (Cq triazole), 172.0 (CO amide).

(R)—N-(1-(4-(4-methylbenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 33)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.25 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 1.73 (2H, m, CH₂—CH₂—CH₂-phenyl), 2.23 (3H, s, CH₃ p-methylbenzyl), 2.49-2.54 (4H, m, CH₂—CH₂—CH ₂-phenyl), 3.33 (2H, m, CH₂ βTrp), 5.04 (2H, s,CH₂-p-methylbenzyl), 5.16 (1H, m, CH αTrp), 6.74 (2H, d, J_(o)=8 Hz, H₃and H₅ p-methylbenzyl), 6.80 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.98 (1H, t,J_(o)=7 Hz, H₆ Trp), 7.03 (1H, d, J=2 Hz, H₂ Trp), 7.06 (5H, m, CHarphenyl), 7.14 (1H, d, J_(o)=7 Hz, H₄ Trp), 7.20 (2H, d, J_(o)=7 Hz, H₂and H₆ p-methylbenzyl), 7.27 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.01 (3H, brs,NH₂ Aib), 8.95 (1H, d, J=8 Hz, NH amide), 10.80 (1H, d, J=2 Hz, NHindole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 21.0 (CH₃ p-methylbenzyl), 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 24.0(CH₂—CH₂—CH₂-phenyl), 28.5 (CH₂—CH₂—CH₂-phenyl), 29.1 (CH₂ βTrp), 34.7(CH₂—CH₂—CH₂-phenyl), 45.7 (CH αTrp), 45.8 (CH₂-p-methylbenzyl), 56.8(Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.7 (C₅Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.2 (C₄ phenyl), 126.4 (C₃ andC₅ p-methylbenzyl), 127.3 (C₉ Trp), 128.7 (C₂, C₃, C₅ and C₆ phenyl),129.8 (C₂ and C₆ p-methylbenzyl), 133.0 (C₁ p-methylbenzyl), 136.4 (C₈Trp), 137.5 (C₄ p-methylbenzyl), 141.7 (C₁ phenyl), 154.8 (Cq triazole),171.9 (CO Aib).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 34)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.25 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 2.23 (3H, s, CH₃-p-methylbenzyl), 2.84-2.97 (4H, m, CH ₂—CH ₂-indole), 3.32 (2H, m, CH₂βTrp), 5.04 (2H, s, CH ₂-p-methylbenzyl), 5.16 (1H, m, CH αTrp),6.79-6.86 (4H, m, CH ar p-methylbenzyl), 6.99-7.05 (4H, m, H₅ and H₆indole, H₅ and H₆ Trp), 7.08 (3H, m, H₂ indole, H₂ and H₄ Trp),7.25-7.30 (3H, m, H₄ and H₇ indole, H₇ Trp), 8.00 (3H, brs, NH₂ Aib),8.94 (1H, d, J=8 Hz, NH amide), 10.76 (1H, s, NH indole), 10.78 (1H, s,NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 21.0 (CH₃-p-methylbenzyl), 22.8 (CH₂—CH₂-indole), 23.8 (CH₃ Aib),23.9 (CH₃ Aib), 25.9 (CH₂—CH₂-indole), 28.5 (CH₂ βTrp), 45.7(CH₂-p-methylbenzyl and CH αTrp), 56.7 (Cq Aib), 109.9 (C₃ Trp), 111.8(C₇ indole and C₇ Trp), 113.4 (C₃ indole), 118.1 (C₄ Trp), 118.3 (C₄indole), 118.5 (C₅ indole), 118.7 (C₅ Trp), 120.9 (C₆ indole and C₆Trp), 121.3 (C₂ indole and C₂ Trp), 126.3 (C₃ and C₅ p-methylbenzyl),127.2 (C₉ indole), 127.3 (C₉ Trp), 129.8 (C₂ and C₆ p-methylbenzyl),133.1 (C₁ p-methylbenzyl), 135.8 (C₈ indole, C₈ Trp), 136.4 (C₄p-methylbenzyl), 154.8 (Cq triazole), 155.0 (Cq triazole), 171.9 (COAib).

(R)—N-(1-(4-(4-methylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 37)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.25 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 2.23 (3H, s, CH₃p-methylbenzyl), 2.83 (4H, m, CH ₂—CH ₂-phenyl), 3.32 (2H, m, CH₂ βTrp),5.05 (2H, s, CH₂-p-methylbenzyl), 5.18 (1H, m, CH αTrp), 6.75 (2H, d,J_(o)=8 Hz, H₃ and H₅ p-methylbenzyl), 6.82 (1H, t, J_(o)=8 Hz, H₅ Trp),6.99 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.02-7.11 (6H, m, H₂ Trp and CHarphenyl), 7.15 (1H, d, J_(o)=7 Hz, H₄ Trp), 7.20 (2H, d, J_(o)=7 Hz, H₂and H₆ p-methylbenzyl), 7.28 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.01 (3H, brs,NH₂ Aib), 8.93 (1H, d, J=8 Hz, NH amide), 10.77 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 21.0 (CH₃ p-methylbenzyl), 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 26.5(CH₂—CH₂-phenyl), 29.1 (CH₂ βTrp), 32.7 (CH₂—CH₂-phenyl), 45.7 (CH αTrpand CH₂-p-methylbenzyl), 56.8 (Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp),118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.8 (C₂ Trp), 126.4(C₃ and C₅ p-methylbenzyl), 126.6 (C₄ phenyl), 127.3 (C₉ Trp), 128.7(C₂, C₃, C₅ and C₆ phenyl), 129.8 (C₂ and C₆ p-methylbenzyl), 133.0 (C₁p-methylbenzyl), 136.4 (C₈ Trp), 137.5 (C₄ p-methylbenzyl), 140.9 (C₁phenyl), 154.5 (Cq triazole), 154.9 (Cq triazole), 171.9 (CO amide).

(R)—N-(1-(5-benzyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 39)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.23 (3H, s, CH₃ Aib), 1.27 (3H, s, CH₃ Aib), 3.34 (1H, dd, J=14Hz and 6 Hz, CH₂ βTrp), 3.43 (1H, dd, J=14 Hz and 9 Hz, CH₂ βTrp), 4.13(2H, s, CH ₂-benzyl), 5.22 (1H, s, CH αTrp), 5.35 (2H, s,CH₂-o-pyridyl), 6.80 (1H, t, J_(o)=8 Hz, H₅ Trp), 6.92 (1H, t, J_(o)=8Hz, H₅ pyridyl), 6.97 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.04 (1H, d, J_(o)=8Hz, H₄ Trp), 7.07 (1H, d, J=2 Hz, H₂ Trp), 7.10-7.16 (5H, m, CHarbenzyl), 7.19 (1H, s, H₃ o-pyridyl), 7.26 (1H, d, J_(o)=8 Hz, H₇ Trp),7.57 (1H, t, J_(o)=9 Hz, H₄ o-pyridyl), 8.16 (3H, brs, NH₂ Aib), 8.36(1H, d, J_(αβ)=5 Hz, H₆ o-pyridyl), 9.01 (1H, d, J=8 Hz, NH amide),10.85 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.4 (CH₃ Aib), 23.7 (CH₃ Aib), 28.6 (CH₂ βTrp), 30.4(CH₂-benzyl), 45.7 (CH αTrp), 47.7 (CH₂-o-pyridyl), 56.7 (Cq Aib), 109.8(C₃ Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.6 (C₅ Trp), 121.2 (C₆Trp), 121.7 (C₃ o-pyridyl), 123.3 (C₅ o-pyridyl), 124.8 (C₂ Trp), 127.1(C₄ benzyl), 127.3 (C₉ Trp), 128.8 (C₂ and C₆ benzyl), 129.0 (C₃ and C₅benzyl), 135.6 (C₁ benzyl), 136.4 (C₈ Trp), 137.5 (C₄ o-pyridyl), 149.5(C₆ o-pyridyl), 154.1 (Cq triazole), 154.2 (Cq triazole), 155.7 (C₂o-pyridyl), 172.0 (CO amide).

(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 43)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.10 (3H, t, J=8 Hz, CH ₃—CH₂ p-ethylbenzyl), 1.25 (3H, s, CH₃Aib), 1.28 (3H, s, CH₃ Aib), 2.53 (2H, q, J=8 Hz, CH ₃—CH₂p-ethylbenzyl), 2.83 (4H, m, CH ₂—CH ₂-phenyl), 3.34 (2H, m, CH₂ βTrp),5.07 (2H, s, CH ₂-p-ethylbenzyl), 5.19 (1H, m, CH αTrp), 6.77 (2H, d,J_(o)=8 Hz, H₃ and H₅ p-ethylbenzyl), 6.81 (1H, t, J_(o)=7 Hz, H₅ Trp),6.99 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.05-7.10 (7H, m, CHar phenyl, H₂ andH₆ p-ethylbenzyl), 7.13 (1H, d, J=2 Hz, H₂ Trp), 7.20 (1H, d, J_(o)=7Hz, H₄ Trp), 7.28 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.03 (3H, brs, NH₂ Aib),8.94 (1H, d, J=8 Hz, NH amide), 10.79 (1H, s NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 15.9 (CH₃—CH₂ p-ethylbenzyl), 23.5 (CH₃ Aib), 23.8 (CH₃ Aib),26.5 (CH₂—CH₂-phenyl), 28.1 (CH₃—CH₂ p-ethylbenzyl), 29.1 (CH₂ βTrp),32.7 (CH₂—CH₂-phenyl), 45.7 (CH αTrp), 45.8 (CH₂-p-ethylbenzyl), 56.8(Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.7 (C₅Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.5 (C₃ and C₅ p-ethylbenzyl),126.6 (C₄ phenyl), 127.3 (C₉ Trp), 128.6 (C₂ and C₆ p-ethylbenzyl, C₂,C₃, C₅ and C₆ phenyl), 133.1 (C₁ p-ethylbenzyl), 136.5 (C₈ Trp), 140.8(C₁ phenyl), 143.8 (C₄ p-ethylbenzyl), 154.6 (Cq triazole), 154.9 (Cqtriazole), 171.9 (CO amide).

(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide(Compound 44)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.42 (m, 2H, H₃ and H₅ piperidyl), 1.55 (m, 1H, H₅ piperidyl),2.23 (m, 1H, H₄ piperidyl), 2.75 (m, 5H, H₂ piperidyl and CH ₂—CH₂-phenyl), 3.04 (m, 1H, H₆ piperidyl), 3.13 (m, 1H, H₂ piperidyl), 3.32(m, 2H, CH₂ βTrp), 3.66 (s, 3H, OCH₃), 4.97 (m, 2H,CH₂-p-methoxybenzyl), 5.23 (m, 1H, CH αTrp), 6.70 (s, 4H, CHarp-methoxybenzyl), 6.87 (t, 1H, J_(o)=8 Hz, H₅ Trp), 7.00 (m, 2H, H₂ andH₆ Trp), 7.07 (d, 2H, J_(o)=8 Hz, H₂ and H₆ phenyl), 7.14 (d, 1H,J_(o)=7 Hz, H₄ Trp), 7.18-7.30 (m, 4H, H₇ Trp, H₃, H₄ and H₅ phenyl),8.16 and 8.46 (2 m, 2H, NH piperidyl TFA salt), 8.66 (d 1H, J=8 Hz, NHamide), 10.75 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 24.9 (C₃ piperidyl), 25.4 (C₅ piperidyl), 26.5 (CH₂—CH₂-phenyl),29.2 (CH₂ βTrp), 32.7 (CH₂—CH₂-phenyl), 38.7 (C₄ piperidyl), 42.7 (C₂and C₆ piperidyl), 44.7 (CH Trp), 45.3 (CH₂-p-methoxybenzyl), 55.5(OCH₃), 110.2 (C₃ Trp), 111.7 (C₇ Trp), 114.4 (C₃ and C₅p-methoxybenzyl), 118.5 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.4(C₂ Trp), 126.5 (C₂ and C₆ phenyl), 127.5 (C₉ Trp), 127.8 (C₁, C₂ and C₆p-methoxybenzyl), 128.7 (C₃, C₄ and C₅ phenyl), 136.4 (C₈ Trp), 140.8(C₁ phenyl), 155.3 (Cq triazole), 155.4 (Cq triazole), 159.1 (C₄p-methoxybenzyl), 173.1 (CO amide).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide(Compound 45)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.41 (m, 2H, H₃ and H₅ piperidyl), 1.54 (dd, 1H, J=13 Hz and 2Hz, H₅ piperidyl), 2.23 (m, 1H, H₄ piperidyl), 2.72 (m, 2H, H₂ and H₆piperidyl), 2.77-2.93 (m, 4H, CH ₂—CH ₂-indole), 3.06 (m, 2H, H₂ and H₆piperidyl), 3.32 (m, 2H, CH₂ βTrp), 3.65 (s, 3H, OCH₃), 4.94 (s, 2H,CH₂-p-methoxybenzyl), 5.22 (m, 1H, CH αTrp), 6.68 (s, 4H, CHarp-methoxybenzyl), 6.87 (m, 3H, H₅ and H₆ Trp, H₅ indole), 6.98 (m, 4H,H₂ and H₆ indole, H₂ and H₄ Trp), 7.20-7.33 (m, 3H, H₄ and H₇ indole, H₇Trp), 8.15 and 8.46 (2 m, 2H, NH piperidyl TFA salt), 8.64 (d, 1H, J=8Hz, NH amide), 10.74 (s, 2H, NH indole and NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.9 (CH₂—CH₂-indole), 24.9 (C₃ piperidyl), 25.4 (C₅ piperidyl),26.0 (CH₂—CH₂-indole), 29.3 (CH₂ βTrp), 39.1 (C₄ piperidyl), 42.7 (C₂and C₆ piperidyl), 44.7 (CH αTrp), 45.3 (CH₂-p-methoxybenzyl), 55.5(OCH₃), 109.5 (C₃ Trp), 111.7 (C₇ indole and C₇ Trp), 113.5 (C₃ indole),114.4 (C₃ and C₅ p-methoxybenzyl), 118.5 (C₄ indole and C₄ Trp), 118.6(C₅ indole and C₅ Trp), 121.2 (C₆ indole), 121.3 (C₆ Trp), 122.9 (C₂indole and C₂ Trp), 127.2 (C₉ indole), 127.6 (C₉ Trp, C₂ and C₆p-methoxybenzyl), 127.9 (C₁ p-methoxybenzyl), 136.4 (C₈ Trp), 136.6 (C₈indole), 154.9 (Cq triazole), 155.2 (Cq triazole), 159.0 (C₄p-methoxybenzyl), 173.0 (CO amide).

(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide(Compound 50)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.78 (m, 4H, CH ₂—CH ₂-phenyl), 3.26 (1H, dd, J=14 Hz and 7 Hz,CH₂ βTrp), 3.39 (m, 3H, CH₂ βTrp and CH ₂—NH₂), 3.65 (s, 3H, OCH₃), 4.95(m, 2H, CH₂-p-methoxybenzyl), 5.20 (m, 1H, CH αTrp), 6.63 (s, 4H, CHarp-methoxybenzyl), 6.86 (t, 1H, J_(o)=7 Hz, H₅ Trp), 6.99 (s, 1H, H₂Trp), 7.02 (t, 1H, J_(o)=7 Hz, H₆ Trp), 7.10 (m, 2H, H₂ and H₆ phenyl),7.15 (d, 1H, J_(o)=7 Hz, H₄ Trp), 7.23 (m, 3H, H₃, H₄ and H₅ Trp), 7.31(d, 1H, J_(o)=8 Hz, H₇ Trp), 7.95 (brs, 3H, NH₂ Gly, TFA salt), 9.20 (d,1H, J=8 Hz, NH amide), 10.82 (s, 1H, NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 26.5 (CH₂—CH₂-phenyl), 29.8 (CH₂ βTrp), 32.7 (CH₂—CH₂-phenyl),39.0 (CH₂—NH₂), 45.3 (CH₂-p-methoxybenzyl), 45.4 (CH αTrp), 55.4 (OCH₃),109.7 (C₃ Trp), 111.8 (C₇ Trp), 114.5 (C₃ and C₅ p-methoxybenzyl), 118.3(C₄ Trp), 118.9 (C₅ Trp), 121.4 (C₆ Trp), 124.6 (C₂ Trp), 126.5 (C₂ andC₆ phenyl), 127.3 (C₉ Trp), 127.7 (C₁ p-methoxybenzyl), 127.8 (C₂ and C₆p-methoxybenzyl), 128.7 (C₃, C₄ and C₅ phenyl), 136.4 (C₈ Trp), 140.9(C₁ phenyl), 154.3 (Cq triazole), 154.8 (Cq triazole), 159.0 (C₄p-methoxybenzyl), 166.1 (CO amide).

(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide(Compound 51)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.77-2.88 (m, 4H, CH ₂—CH ₂-phenyl), 3.37 (m, 2H, CH₂ βTrp), 3.64(s, 3H, OCH₃), 3.74 (m, 2H, CH₂-o-pyridyl), 5.03 (m, 2H, CH₂-p-methoxybenzyl), 5.24 (m, 1H, CH αTrp), 6.65 (s, 4H, CHarp-methoxybenzyl), 6.85 (t, 1H, J_(o)=7 Hz, H₅ Trp), 7.01 (m, 2H, H₂ andH₆ Trp), 7.08 (d, 2H, J_(o)=7 Hz, H₂ and H₆ phenyl), 7.15 (d, 1H,J_(o)=7 Hz, H₄ Trp), 7.21 (m, 3H, H₃, H₄ and H₅ phenyl), 7.27-7.36 (m,2H, H₇ Trp and H₃ o-pyridyl), 7.58 (t, 1H, J=6 Hz, H₅ o-pyridyl), 8.04(t, 1H, J_(o)=8 Hz, H₄ o-pyridyl), 8.62 (d, 1H, J_(αβ)=5 Hz, H₆o-pyridyl), 9.17 (d, 1H, J=8 hz, NH amide), 10.81 (s, 1H, NH indoleTrp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 26.4 (CH₂—CH₂-phenyl), 29.2 (CH₂ βTrp), 32.4 (CH₂—CH₂-phenyl),41.7 (CH₂-o-pyridyl), 45.3 (CH αTrp), 45.7 (CH₂-p-methoxybenzyl), 55.5(OCH₃), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 114.4 (C₃ and C₅p-methoxybenzyl), 118.4 (C₄ Trp), 118.8 (C₅ Trp), 121.4 (C₆ Trp), 124.1(C₃ o-pyridyl), 124.6 (C₂ Trp), 126.4 (C₅ o-pyridyl), 126.6 (C₂ and C₆phenyl), 127.2 (C₉ Trp), 127.4 (C₁ p-methoxybenzyl), 127.9 (C₂ and C₆p-methoxybenzyl), 128.7 (C₃, C₄ and C₅ phenyl), 136.4 (C₈ Trp), 140.5(C₁ phenyl), 142.1 (C₄ o-pyridyl), 145.3 (C₆ o-pyridyl), 153.0 (C₂o-pyridyl), 154.5 (Cq triazole), 155.3 (Cq triazole), 159.1 (C₄p-methoxybenzyl), 167.9 (CO amide).

(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide(Compound 64)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.83 (m, 2H, CH ₂—CH₂-phenyl), 2.90 (m, 2H, CH₂—CH ₂-phenyl),3.48 (m, 2H, CH₂ βTrp), 3.57 (s, 3H, OCH₃), 3.61 (s, 3H, OCH₃), 4.97 (d,1H, J=17 Hz, CH₂-o,p-dimethoxybenzyl), 5.09 (d, 1H, J=17 Hz,CH₂-o,p-dimethoxybenzyl), 5.56 (m, 1H, CH αTrp), 6.18 (dd, 1H, J_(o)=8Hz and J_(m)=2 Hz, H₅ o,p-dimethoxybenzyl), 6.41 (d, 1H, J_(m)=2 Hz, H₃o,p-dimethoxybenzyl), 6.55 (d, 1H, J_(o)=8 Hz, H₆ o,p-dimethoxybenzyl),6.87 (t, 1H, J_(o)=8 Hz, H₅ Trp), 7.01 (t, 1H, J_(o)=8 Hz, H₆ Trp), 7.08(m, 3H, H₂ Trp, H₂ and H₆ phenyl), 7.14 (d, 1H, J_(o)=7 Hz, H₄ Trp),7.19-7.31 (m, 4H, H₇ Trp, H₃, H₄ and H₅ phenyl), 7.56 (t, 1H, J=8 Hz, NHamide), 7.91 (m, 2H, H₄ and H₅ o-pyridyl), 8.57 (d, 1H, J_(αβ)=5 Hz, H₆o-pyridyl), 9.16 (d, 1H, J_(o)=8 Hz, H₃ o-pyridyl), 10.80 (s, 1H, NHindole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 26.2 (CH₂—CH₂-phenyl), 28.8 (CH₂ βTrp), 32.1 (CH₂—CH₂-phenyl),43.0 (CH₂-o,p-dimethoxybenzyl), 45.5 (CH αTrp), 55.6 (OCH₃), 55.8(OCH₃), 98.9 (C₃ o,p-dimethoxybenzyl), 105.0 (C₅ o,p-dimethoxybenzyl),109.5 (C₃ Trp), 111.8 (C₇ Trp), 114.4 (C₁ o,p-dimethoxybenzyl), 118.4(C₄ Trp), 118.8 (C₅ Trp), 121.4 (C₆ Trp), 122.4 (C₃ o-pyridyle), 124.4(C₂ Trp), 126.7 (C₆ o,p-dimethoxybenzyl), 127.2 (C₅ o-pyridyle), 127.5(C₉ Trp), 128.6-128.8 (C₂, C₃, C₄, C₅ and C₆ phenyl), 136.4 (C₈ Trp),138.1 (C₄ o-pyridyle), 140.2 (C₁ phenyl), 148.8 (C₆ o-pyridyle), 149.3(C₂ o-pyridyle), 155.2 (Cq triazole), 155.4 (Cq triazole), 157.9 (C₂o,p-dimethoxybenzyl), 161.0 (C₄ o,p-dimethoxybenzyl), 163.9 (CO amide).

(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide(Compound 66)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.87 (m, 4H, CH ₂—CH ₂-phenyl), 3.51 (m, 2H, CH₂ βTrp), 3.58 (s,3H, OCH₃), 3.59 (s, 3H, OCH₃), 4.97 (d, 1H, J=17 Hz, CH₂-o,p-dimethoxybenzyl), 5.08 (d, 1H, J=17 Hz, CH₂-o,p-dimethoxybenzyl),5.56 (s, 1H, CH αTrp), 6.10 (dd, 1H, J_(o)=8 Hz and J_(m)=2 Hz, H₅o,p-dimethoxybenzyl), 6.36 (d, 1H, J_(m)=2 Hz, H₃ o,p-dimethoxybenzyl),6.40 (d, 1H, J_(o)=8 Hz, H₆ o,p-dimethoxybenzyl), 6.87 (t, 1H, J_(o)=8Hz, H₅ Trp), 7.00 (t, 1H, J_(o)=7 Hz, H₆ Trp), 7.09 (m, 3H, H₂ Trp, H₂and H₆ phenyl), 7.15 (d, 1H, J_(o)=7 Hz, H₄ Trp), 7.19-7.28 (m, 3H, H₃,H₄ and H₅ phenyl), 7.36 (d, 1H, J_(o)=8 Hz, H₇ Trp), 8.61 (t, 1H, J=2Hz, H₃ o-pyrazinyl), 8.78 (d, 1H, J=2 Hz, H₅ o-pyrazinyl), 8.94 (d, 1H,J=1 Hz, H₆ o-pyrazinyl), 9.26 (d, 1H, J=8 Hz, NH amide), 10.78 (s, 1H,NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 26.1 (CH₂—CH₂-phenyl), 28.4 (CH₂ βTrp), 32.1 (CH₂—CH₂-phenyl),42.9 (CH₂-o,p-dimethoxybenzyl), 45.5 (CH αTrp), 55.5 (OCH₃), 55.8(OCH₃), 98.7 (C₃ o,p-dimethoxybenzyl), 104.9 (C₅ o,p-dimethoxybenzyl),109.7 (C₃ o,p-dimethoxybenzyl), 111.8 (C₇ Trp), 114.5 (C₁o,p-dimethoxybenzyl), 118.5 (C₄ Trp), 118.8 (C₅ Trp), 121.4 (C₆ Trp),124.4 (C₂ Trp), 126.7 (C₆ o,p-dimethoxybenzyl), 127.5 (C₉ Trp), 128.1(C₄ phenyl), 128.7-128.8 (C₂, C₃, C₅ and C₆ phenyl), 136.4 (C₈ Trp),140.3 (C₁ phenyl), 141.2 (C₆ o,p-dimethoxybenzyl), 144.2 (C₂o-pyrazinyl), 144.3 (C₃ o-pyrazinyl), 146.8 (C₅ o-pyrazinyl), 155.2 (Cqstriazole), 157.7 (C₂ o,p-dimethoxybenzyl), 160.7 (CO amide), 162.9 (C₄o,p-dimethoxybenzyl).

(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide(Compound 70)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.40 (m, 1H, H₃ Pro), 1.53 (m, 1H, H₄ Pro), 1.71 (m, 1H, H₄ Pro),2.09 (m, 1H, H₃ Pro), 2.90 (m, 4H, CH ₂—CH ₂-indole), 3.06 (t, 2H, J=6Hz, H₅ Pro), 3.28 (m, 2H, CH₂ βTrp), 3.40(s, 3H, OCH₃), 3.80(s, 3H,OCH₃), 3.80(m, 1H, CH αPro), 4.80(d, 1H, J=17 Hz,CH₂-o,p-dimethoxybenzyl), 5.4 (d, 1H, J=17 Hz, CH₂-o,p-dimethoxybenzyl),5.1 (m, 1H, CH αTrp), 6.26 (dd, 1H, J_(o)=8 Hz and J_(m)=2 Hz, H₅o,p-dimethoxybenzyl), 6.38 (d, 1H, J_(o)=8 Hz, H₆ o,p-dimethoxybenzyl),6.53 (d, 1H, J_(m)=2 Hz, H₃ o,p-dimethoxybenzyl), 6.84 (t, 1H, H₅indole), 6.91 (t, 1H, J_(o)=8 Hz, H₅ Trp), 6.93-7.07 (m, 4H, H₂ and H₆indole, H₂ and H₆ Trp), 7.16 (d, 1H, J_(o)=8 Hz, H₄ Trp), 7.29 (m, 3H,H₄ and H₇ indole, H₇ Trp), 8.39 and 9.10 (2 m, 2H, NH Pro TFA salt),9.22 (d, 1H, J=8 Hz, NH amide), 10.76 (s, 1H, NH indole), 10.80 (s, 1H,NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.9 (CH₂—CH₂-indole), 23.5 (C₄ Pro), 25.8 (CH₂—CH₂-indole), 29.6(CH₂ βTrp), 29.8 (C₃ Pro), 41.9 (CH₂-o,p-dimethoxybenzyl), 45.2 (CHαTrp), 46.0 (C₅ Pro), 55.7 (OCH₃), 55.9 (OCH₃), 59.3 (CH αPro), 99.0 (C₃o,p-dimethoxybenzyl), 105.1 (C₅ o,p-dimethoxybenzyl), 109.7 (C₃ Trp),111.8 (C₇ indole and C₇ Trp), 113.4 (C₃ indole), 115.6 (C₁o,p-dimethoxybenzyl), 118.4 (C₄ indole and C₄ Trp), 118.7 (C₅ indole andC₅ Trp), 121.4 (C₆ indole and C₆ Trp), 123.0 (C₂ indole and C₂ Trp),127.2 (C₉ indole), 127.3 (C₉ Trp), 128.1 (C₆ o,p-dimethoxybenzyl), 136.5(C₈ Trp), 136.6 (C₈ indole), 155.0 (Cq triazole), 157.8 (C₂o,p-dimethoxybenzyl), 160.9 (C₄ o,p-dimethoxybenzyl), 168.1 (CO amide).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide(Compound 71)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 3.01 (m, 2H, CH ₂—CH₂-indole), 3.10 (m, 2H, CH₂—CH ₂-indole),3.51 (m, 2H, CH₂ βTrp), 3.55 (s, 3H, OCH₃), 3.57 (s, 3H, OCH₃), 5.15 (d,2H, J=7 Hz, CH₂-o,p-dimethoxybenzyl), 5.63 (m, 1H, CH αTrp), 6.08 (dd,1H, J_(o)=8 Hz and J_(m)=2 Hz, H₅ o,p-dimethoxybenzyl), 6.35 (d, 1H,J_(m)=2 Hz, H₃ o,p-dimethoxybenzyl), 6.53 (d, 1H, J_(o)=8 Hz, H₆o,p-dimethoxybenzyl), 6.89 (m, 2H, H₅ indole and H₅ Trp), 6.99 (m, 2H,H₆ indole and H₆ Trp), 7.08 (m, 2H, H₂ indole and H₂ Trp), 7.29 (m, 3H,H₄ Trp, H₄ and H₇ indole), 7.41 (d, 1H, J_(o)=8 Hz, H₇ Trp), 8.61 (t,1H, J=2 Hz, H₃ o-pyrazine), 8.79 (d, 1H, J=2 Hz, H₅ o-pyrazine), 8.94(d, 1H, J=1 Hz, H₆ o-pyrazine), 9.43 (d, 1H, J=8 Hz, NH amide), 10.84(s, 2H, NH indole and NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.0 (CH₂—CH₂-indole), 25.3 (CH₂—CH₂-indole), 27.9 (CH₂ βTrp),44.1 (CH₂-o,p-dimethoxybenzyl), 45.5 (CH αTrp), 55.5 (OCH₃), 55.8(OCH₃), 98.8 (C₃ o,p-dimethoxybenzyl), 104.9 (C₅ o,p-dimethoxybenzyl),109.3 (C₃ Trp), 111.8 (C₇ indole and C₇ Trp), 112.1 (C₃ indole), 113.4(C₁ o,p-dimethoxybenzyl), 118.4 (C₄ indole), 118.5 (C₄ Trp), 118.8 (C₅indole and C₅ Trp), 121.5 (C₆ indole and C₆ Trp), 127.0 (C₉ indole),127.4 (C₉ Trp), 136.4 (C₈ Trp), 136.6 (C₈ indole), 141.2 (C₆o-pyrazine), 144.1 (C₂ o-pyrazine), 144.3 (C₃ o-pyrazine), 146.8 (C₅o-pyrazine), 155.4 (Cq triazole), 156.0 (Cq triazole), 157.8 (C₂o,p-dimethoxybenzyl), 161.0 (CO amide), 163.2 (C₄ o,p-dimethoxybenzyl).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide(Compound 73)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.94 (m, 4H, CH ₂—CH ₂-indole), 3.47 (m, 2H, CH₂ βTrp), 3.57 (s,3H, OCH₃), 3.60 (s, 3H, OCH₃), 5.05 (m, 2H, CH₂-o,p-dimethoxybenzyl),5.56 (m, 1H, CH αTrp), 6.14 (dd, 1H, J_(o)=8 Hz and J_(m)=2 Hz, H₅o,p-dimethoxybenzyl), 6.41 (d, 1H, J_(m)=2 Hz, H₃ o,p-dimethoxybenzyl),6.52 (d, 1H, J_(o)=8 Hz, H₆ o,p-dimethoxybenzyl), 6.88 (t, 2H, J_(o)=7Hz, H₅ indole and H₅ Trp), 6.99 (t, 1H, J_(o)=8 Hz, H₆ Trp), 7.01 (t,1H, J_(o)=8 Hz, H₆ indole), 7.04 (d, 1H, J=2 Hz, H₂ Trp), 7.07 (d, 1H,J=2 Hz, H₂ indole), 7.27-7.33 (m, 4H, H₄ and H₇ Trp, H₄ and H₇ indole),7.55 (m, 1H, NH amide), 7.90 (m, 2H, H₄ and H₅ o-pyridyl), 8.57 (d, 1H,J_(αβ)=4 Hz, H₆ o-pyridyl), 9.15 (d, 1H, J=8 Hz, H₃ o-pyridyl), 10.78(brs, 2H N indole and NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.3 (CH₂—CH₂-indole), 25.6 (CH₂—CH₂-indole), 28.9 (CH₂ βTrp),43.1 (CH₂-o,p-dimethoxybenzyl), 45.5 (CH αTrp), 55.5 (OCH₃), 55.8(OCH₃), 98.9 (C₃ o,p-dimethoxybenzyl), 105.0 (C₅ o,p-dimethoxybenzyl),109.5 (C₃ Trp), 111.8 (C₇ indole and C₇ Trp), 112.8 (C₃ indole), 114.4(C₁ o,p-dimethoxybenzyl), 118.4 (C₄ indole and C₄ Trp), 118.7 (05indole), 118.8 (C₅ Trp), 121.4 (C₆ indole and C₆ Trp), 122.5 (C₂ indoleand C₃ o-pyridyl), 123.1 (C₂ Trp), 127.1 (C₅ o-pyridyl), 127.2 (C₉indole), 127.5 (C₉ Trp), 128.6 (C₆ o,p-dimethoxybenzyl), 136.4 (C₈ Trp),136.6 (C₈ indole), 139.1 (C₄ o-pyridyl), 146.6 (C₆ o-pyridyl), 150.6 (C₂o-pyridyl), 155.5 (Cq triazole), 155.6 (Cq triazole), 157.8 (C₂o,p-dimethoxybenzyl), 161.0 (C₄ o,p-dimethoxybenzyl), 163.9 (CO amide).

(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine(Compound 74)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.79 (m, 2H, CH ₂—CH₂-indole), 2.86 (m, 2H, CH₂—CH ₂-indole),3.30 (dd, 1H, ³J=14 Hz and 5 Hz, CH ₂ βTrp), 3.38 (dd, 1H, ³J=14 Hz and6 Hz, CH ₂βTrp), 3.62 (s, 3H, OCH₃), 3.63 (s, 3H, OCH₃), 4.47 (d, 1H,³J=17 Hz, CH ₂-o,p-dimethoxybenzyl), 4.59 (d, 1H, ³J=17 Hz, CH₂-o,p-dimethoxybenzyl), 6.11 (dd, 1H, J_(o)=8 Hz and J_(m)=2 Hz, H₅o,p-dimethoxybenzyl), 6.20 (d, 1H, J_(o)=8 Hz, H₆ o,p-dimethoxybenzyl),6.45 (d, 1H, J_(m)=2 Hz, H₃ o,p-dimethoxybenzyl), 6.87 (t, 1H, J_(o)=8Hz, H₅ Trp), 6.91 (t, 1H, J_(o)=8 Hz, H₅ indole), 7.00-7.04 (m, 2H, H₆indole and H₆ Trp), 7.07 (s, 1H, H₂ indole), 7.09 (s, 1H, H₂ Trp),7.17-7.35 (m, 4H, H₄ and H₇ indole, H₄ and H₇ Trp), 8.75 (brs, 3H, NH₂TFA salt), 10.78 (s, 1H, NH indole), 11.00 (s, 1H, NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.9 (CH₂—CH₂-indole), 25.7 (CH₂—CH₂-indole), 29.9 (CH₂ βTrp),41.5 (CH₂-o,p-dimethoxybenzyl), 46.5 (CH αTrp), 55.6 (OCH₃), 55.9(OCH₃), 98.8 (C₃ o,p-dimethoxybenzyl), 105.0 (C₅ o,p-dimethoxybenzyl),107.4 (C₃ Trp), 111.8 (C₇ indole and C₇ Trp), 113.4 (C₃ indole), 115.1(C₁ o,p-dimethoxybenzyl), 118.0 (C₄ indole), 118.4 (C₄ Trp), 118.6 (C₅Trp), 119.0 (C₅ indole), 121.3 (C₆ Trp), 121.6 (C₆ indole), 122.9 (C₂indole), 125.4 (C₂ Trp), 127.1 (C₉ indole and C₉ Trp), 128.5 (C₆o,p-dimethoxybenzyl), 136.5 (C₈ Trp), 136.6 (C₈ indole), 152.3 (Cqtriazole), 155.6 (Cq triazole), 157.6 (C₂ o,p-dimethoxybenzyl), 160.8(C₄ o,p-dimethoxybenzyl).

(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide(Compound 79)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.85 (m, 4H, CH ₂—CH ₂-phenyl), 3.51 (m, 2H, CH₂ βTrp), 3.59 (s,3H, OCH₃), 5.11 (d, 1H, J=17 Hz, CH₂-p-methoxybenzyl), 5.23 (d, 1H, J=17Hz, CH₂-p-methoxybenzyl), 5.51 (m, 1H, CH αTrp), 6.59 (d, 2H, J_(o)=8Hz, H₃ and H₅ p-methoxybenzyl), 6.73 (d, 2H, J_(o)=8 Hz, H₂ and H₆p-methoxybenzyl), 6.87 (t, 1H, J_(o)=8 Hz, H₅ Trp), 7.01 (t, 1H, J_(o)=8Hz, H₆ Trp), 7.06 (m, 2H, H₂ and H₆ phenyl), 7.10 (d, 1H, J=2 Hz, H₂Trp), 7.14 (d, 1H, J_(o)=7 Hz, H₄ Trp), 7.24 (m, 3H, H₃, H₄ and H₅phenyl), 7.34 (d, 1H, J_(o)=8 Hz, H₇ Trp), 7.55 (m, 1H, NH amide), 7.88(m, 2H, H₄ and H₅ o-pyridyl), 8.56 (d, 1H, J_(αβ)=4 Hz, H₆ o-pyridyl),9.20 (d, 1H, J_(o)=8 Hz, H₃ o-pyridyl), 10.80 (s, 1H, NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 26.2 (CH₂—CH₂-phenyl), 28.6 (CH₂ βTrp), 32.1 (CH₂—CH₂-phenyl),45.5 (CH αTrp), 46.2 (CH₂-p-methoxybenzyl), 55.4 (OCH₃), 109.6 (C₃ Trp),111.8 (C₇ Trp), 114.3 (C₃ and C₅ p-methoxybenzyl), 118.5 (C₄ Trp), 118.8(C₅ Trp), 121.4 (C₆ Trp), 122.5 (C₃ o-pyridyl), 124.5 (C₂ Trp), 127.2(C₂ and C₆ phenyl), 127.4 (C₉ Trp and C₁ p-methoxybenzyl), 127.8 (C₅o-pyridyl), 128.7 (C₂ and C₆ p-methoxybenzyl), 128.8 (C₃, C₄ and C₅phenyl), 136.4 (C₆ Trp), 138.1 (C₄ o-pyridyl), 140.3 (C₁ phenyl), 148.7(C₆ o-pyridyl), 149.3 (C₂ o-pyridyl), 155.0 (Cq triazole), 155.3 (Cqtriazole), 159.0 (C₄ p-methoxybenzyl), 164.1 (CO amide).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide(Compound 80)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.95 (m, 4H, CH ₂—CH ₂-indole), 3.48 (m, 2H, CH₂ βTrp), 3.58 (s,3H, OCH₃), 5.16 (m, 2H, CH₂-p-methoxybenzyl), 5.50 (m, 1H, CH αTrp),6.57 (d, 2H, J_(o)=8 Hz, H₃ and H₅ p-methoxybenzyl), 6.72 (d, 2H,J_(o)=8 Hz, H₂ and H₆ p-methoxybenzyl), 6.87 (t, 2H, J_(o)=8 Hz, H₅ Trpand H₅ indole), 6.96-7.07 (m, 5H, H₂ and H₆ indole, H₂, H₄ and H₆ Trp),7.27-7.34 (m, 3H, H₄ and H₇ indole, H₇ Trp), 7.55 (m, 1H, NH amide),7.88 (m, 2H, H₄ and H₅ o-pyridyl), 8.56 (d, 1H, J_(αβ)=4 Hz, H₆o-pyridyl), 9.18 (d, 1H, J_(o)=8 Hz, H₃ o-pyridyl), 10.77 (brs, 2H, NHindole Trp and NH indole).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.4 (CH₂—CH₂-indole), 25.7 (CH₂—CH₂-indole), 28.9 (CH₂ βTrp),45.5 (CH αTrp), 46.2 (CH₂-p-methoxybenzyl), 55.4 (OCH₃), 109.7 (C₃ Trp),111.8 (C₇ Trp and C₇ indole), 112.6 (C₃ indole), 114.3 (C₃ and C₅p-methoxybenzyl), 118.4 (C₄ Trp and C₄ indole), 118.7 (C₅ indole), 118.8(C₅ Trp), 121.4 (C₆ Trp and C₆ indole), 122.4 (C₃ o-pyridyl and C₂indole), 124.5 (C₂ Trp), 126.7 (C₉ indole), 127.1 (C₉ Trp), 127.2 (C₅o-pyridyl), 127.5 (C₁ p-methoxybenzyl), 127.7 (C₂ and C₆p-methoxybenzyl), 136.4 (C₈ Trp), 136.6 (C₈ indole), 138.1 (C₄o-pyridyl), 148.7 (C₆ o-pyridyl), 149.3 (C₂ o-pyridyl), 155.3 (Cqtriazole), 159.0 (C₄ p-methoxybenzyl), 164.0 (CO amide).

(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide(Compound 81)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 2.18 (m, 2H, NH piperazine), 2.96 (m, 6H, H₂, H₅ and H₆piperazine), 3.34 (d, 2H, J=7 Hz, CH₂ βTrp), 3.57 (m, 4H, CH ₂—CH₂-indole), 3.61 (s, 3H, OMe), 3.64 (m, 1H, H₃ piperazine), 4.82 (m, 2H,CH₂-p-methoxybenzyl), 5.40 (m, 1H, CH αTrp), 6.45 (d, 2H, J_(o)=8 Hz, H₃and H₅ p-methoxybenzyl), 6.51 (d, 2H, J_(o)=8 Hz, H₂ and H₆p-methoxybenzyl), 6.65-7.47 (m, 10H, CHar, indole and indole Trp), 8.95(m, 1H, NH amide), 10.88 (d, 1H, J=2 Hz, NH indole), 10.91 (s, 1H, NHindole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.5 (CH₂—CH₂-indole), 25.6 (CH₂—CH₂-indole), 31.3 (CH₂ βTrp),41.9 (CH₂-p-methoxybenzyl), 47.7 (CH αTrp, C₅ and C₆ piperazine), 55.5(OCH₃ and C₂ piperazine), 61.1 (C₃ piperazine), 109.3 (C₃ Trp), 111.7(C₇ indole and C₇ Trp), 114.0 (C₃ indole), 114.3 (C₃ and C₅p-methoxybenzyl), 118.6 (C₄ indole), 118.7 (C₄ Trp), 118.9 (C₅ indoleand C₅ Trp), 121.4 (C₆ indole), 121.5 (C₆ Trp), 123.9 (C₂ indole and C₂Trp), 127.0 (C₉ indole), 127.2 (C₉ Trp), 127.7 (C₁ p-methoxybenzyl),128.1 (C₂ and C₆ p-methoxybenzyl), 136.3 (C₈ Trp), 136.5 (C₈ indole),155.5 (Cq triazole), 162.2 (C₄ p-methoxybenzyl), 171.1 (CO amide).

(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide(Compound 89)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.42 (m, 1H, H₃ Pro), 1.52 (m, 1H, H₄ Pro), 1.72 (m, 1H, H₄ Pro),2.07 (m, 1H, H₃ Pro), 2.94 (m, 4H, CH ₂—CH ₂-indole), 3.05 (t, 2H, J=6Hz, H₅ Pro), 3.30 (m, 2H, CH₂ βTrp), 3.67 (s, 3H, OCH₃), 3.96 (m, 1H, CHαPro), 5.02 (s, 2H, CH₂-p-methoxybenzyl), 5.19 (m, 1H, CH αTrp), 6.73(s, 4H, CHar p-methoxybenzyl), 6.84 (t, 1H, J_(o)=8 Hz, H₅ indole), 6.90(t, 1H, J_(o)=8 Hz, H₅ Trp), 6.93-7.06 (m, 4H, H₂ and H₆ indole, H₂ andH₆ Trp), 7.17 (d, 1H, J_(o)=8 Hz, H₄ Trp), 7.29 (d, 3H, J_(o)=8 Hz, H₄and H₇ indole, H₇ Trp), 8.39 and 9.10 (2 m, 2H, NH Pro TFA salt), 9.25(d, 1H, J=8 Hz, NH amide), 10.76 (s, 1H, NH indole), 10.80 (d, 1H, J=2Hz, NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.8 (CH₂—CH₂-indole), 23.5 (C₄ Pro), 25.8 (CH₂—CH₂-indole), 29.4(CH₂ βTrp), 29.8 (C₃ Pro), 45.2 (CH αTrp), 45.5 (CH₂-p-methoxybenzyl),46.0 (C₅ Pro), 55.5 (OCH₃), 59.3 (CH αPro), 109.6 (C₃ Trp), 111.8 (C₇indole and C₇ Trp), 113.4 (C₃ indole), 114.6 (C₃ and C₅p-methoxybenzyl), 118.4 (C₄ indole), 118.5 (C₄ Trp), 118.7 (C₅ indoleand C₅ Trp), 121.4 (C₆ indole and C₆ Trp), 123.0 (C₂ Trp), 124.7 (C₂indole), 127.2 (C₉ indole), 127.3 (C₉ Trp), 127.7 (C₁ p-methoxybenzyl),127.8 (C₂ and C₆ p-methoxybenzyl), 126.5 (C₈ Trp), 136.6 (C₈ indole),154.8 (Cq triazole), 154.9 (Cq triazole), 159.2 (C₄ p-methoxybenzyl),168.2 (CO amide).

(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide(Compound 90)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.23 (m, 1H, H₃ Pro), 1.52 (m, 1H, H₄ Pro), 1.74 (m, 1H, H₄ Pro),2.08 (m, 1H, H₃ Pro), 2.81 (m, 2H, H₅ Pro), 2.90-3.14 (m, 4H, CH ₂—CH₂-indole), 3.31 (dd, 1H, J=14 Hz and 7 Hz, CH₂ βTrp), 3.41 (dd, 1H, J=14Hz and 8 Hz, CH₂ βTrp), 3.63 (s, 3H, OCH₃), 4.05 (m, 1H, CH αPro), 4.86(s, 2H, CH₂-p-methoxybenzyl), 5.21 (m, 1H, CH αTrp), 6.63 (s, 4H, CHarp-methoxybenzyl), 6.88 (t, 2H, J_(o)=7 Hz, H₅ indole and H₅ Trp), 7.02(m, 4H, H₂ and H₆ indole, H₂ and H₆ Trp), 7.26-7.34 (m, 4H, H₄ and H₇indole, H₄ and H₇ Trp), 8.51 and 9.18 (2 m, 2H, NH Pro, TFA salt), 9.27(d, 1H, J=8 Hz, NH amide), 10.73 (s, 1H, NH indole), 10.80 (s, 1H, NHindole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 22.8 (CH₂—CH₂-indole), 23.8 (C₄ Pro), 25.9 (CH₂—CH₂-indole), 29.7(CH₂ βTrp and C₃ Pro), 45.4 (CH₂-p-methoxybenzyl), 45.8 (CH αTrp), 46.1(C₅ Pro), 55.5 (OCH₃), 59.2 (CH αPro), 109.7 (C₃ Trp), 111.8 (C₇ Trp),111.9 (C₇ indole), 113.4 (C₃ indole), 114.4 (C₃ and C₅ p-methoxybenzyl),118.3 (C₄ indole), 118.5 (C₄ Trp), 118.6 (C₅ indole), 118.9 (C₅ Trp),121.4 (C₆ indole and C₆ Trp), 122.9 (C₂ indole and C₂ Trp), 127.2 (C₉indole), 127.4 (C₉ Trp), 127.6 (C₁, C₂ and C₆ p-methoxybenzyl), 136.5(C₈ Trp), 136.6 (C₈ indole), 154.4 (Cq triazole), 155.0 (Cq triazole),159.1 (C₄ p-methoxybenzyl), 168.3 (CO amide).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 92)

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.28 (3H, s, CH₃ Aib), 1.30 (3H, s, CH₃ Aib), 2.90 (2H, m, CH₂—CH₂-indole), 3.00 (2H, m, CH₂—CH₂ -indole), 3.37 (2H, m, CH₂ βTrp),5.10 (2H, s, CH₂ 4-bromobenzyl), 5.13 (1H, m, CαH Trp), 6.75 (2H, d,J=8.1, H₂, H₆ 4-bromobenzyl), 6.88 (1H, t, J=7.3, H₅ Trp), 6.93 (1H, t,J=7.5, H₅ indole), 7.03 (1H, t, J=7.0, H₆ Trp), 7.05 (1H, H₆ indole),7.07 (1H, d, J=1.7, H₂ indole), 7.09 (1H, d, J=1.8, H₂ Trp), 7.12 (1H,d, J=8.2, H₄ Trp), 7.28 (1H, d, J=7.9, H₄ indole), 7.32 (2H, d, J=8.2,H₇ Trp, H₇ indole), 7.41 (2H, d, J=8.1, H₃, H₅ 4-bromobenzyl), 8.01 (2H,s, NH₂ Aib), 8.95 (1H, d, J=7.9, NH Trp), 10.77 (1H, brs, NH indole),10.80 (1H, brs, NH indole Trp).

¹³C NMR (400 MHz,DMSO-d⁶):

δ(ppm) 22.4 (CH₂—CH_(.□)-indole), 23.1 (CH₃ Aib), 23.4 (CH₃ Aib), 25.4(CH₂—CH_(.□)indole), 28.7 (Cβ Trp), 44.8 (CH₂ 4-bromobenzyl), 45.2 (CαTrp,), 56.3 (Cq Aib), 109.4 (C₃ Trp), 111.3 (C₇ Trp, C₇ indole), 113.0(C₃ indole), 117.8 (C₄ Trp), 118.0 (C₄ indole), 118.2 (C₅ indole), 118.3(C₅ Trp), 120.8 (C₄ 4-bromobenzyl), 120.9 (C₆ Trp, C₆ indole), 122.5 (C₂indole), 124.4 (C₂ Trp), 126.7 (C₉ Indole), 126.8 (C₉ Trp), 128.0 (C₂,C₆ 4-bromobenzyl), 131.6 (C₃, C₅ 4-bromobenzyl), 135.1 (C₁4-bromobenzyl), 136.1 (C₈ Trp, C₈ indole), 154.2 (Cq triazole), 154.5(Cq triazole), 171.4 (CO Aib).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide(Compound 93)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.18 (3H, s, CH₃ Aib), 1.27 (3H, s, CH₃ Aib), 2.91 (4H, m, CH₂—CH ₂-indole), 3.19 (2H, m, CH₂ βPhe), 3.69 (3H, s, OCH₃), 5.05 (2H, m,CH₂-p-methoxybenzyl), 5.20 (1H, m, CH αPhe), 6.82 (2H, d, J_(o)=8 Hz, H₃and H₅ p-methoxybenzyl), 6.88 (2H, d, J_(o)=8 Hz, H₂ and H₆p-methoxybenzyl), 6.92 (1H, t, J_(o)=8 Hz, H₅ indole), 7.02 (1H, t,J_(o)=7 Hz, H₆ indole), 7.03 (1H, d, J=2 Hz, H₂ indole), 7.11-7.20 (5H,m, CHar Phe), 7.29 (2H, d, J_(o)=8 Hz, H₄ and H₇ indole), 7.99 (3H, brs,NH₂ Aib), 8.93 (1H, d, J=8 Hz, NH amide), 10.77 (1H, s, NH indole).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 22.8 (CH₂—CH₂-indole), 23.5 (CH₃ Aib), 23.9 (CH₃ Aib), 25.9(CH₂—CH₂-indole), 38.7 (CH₂ βPhe), 45.7 (CH₂-p-methoxybenzyl), 46.4 (CHαPhe), 55.6 (OCH₃), 56.8 (Cq Aib), 111.8 (C₇ indole), 113.4 (C₃ indole),114.7 (C₃ and C₅ p-methoxybenzyl), 118.5 (C₄ Trp), 118.6 (C₅ Trp), 121.4(C₆ Trp), 123.0 (C₂ Trp), 127.0 (C₄ phenyl), 127.2 (C₉ indole), 127.9(C₁ p-methoxybenzyl), 128.1 (C₂ and C₆ phenyl), 128.5 (C₃ and C₅phenyl), 129.8 (C₂ and C₆ p-methoxybenzyl), 136.6 (C₈ indole), 137.7 (C₁phenyl), 155.2 (Cq triazole), 154.4 (Cq triazole), 159.3 (C₄p-methoxybenzyl), 171.7 (CO Aib).

(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 95)

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.29 (3H, s, CH₃ Aib), 1.35 (3H, s, CH₃ Aib), 2.85 (1H, m, 1HN—CH₂—CH₂ —In), 2.89 (1H, m, 1H, —N—CH₂—CH₂ —In), 3.28 (1H, dd, J=14.2,J=6.8, 1H C₂β Trp), 3.40 (1H, dd, J=14.2, J=8.4, 1H C₂β Trp), 4.10 (2H,m, —N—CH₂ —CH₂—In), 5.25 (1H, m, CHα Trp), 6.85 (1H, d, J=2.0, H₂indole), 6.90-6.98 (2H, m, H₅ indole), 7.01 (1H, d, J=2.0, H₂ indole),7.02-7.12 (2H, m, H₆ indole), 7.30 (1H, d, J=8.2, H₇ indole), 7.33 (1H,d, J=8.3, H₇ indole), 7.40 (1H, d, J=7.9, H₄ indole), 7.47 (1H, d,J=7.8, H₄ indole), 8.04 (2H, brs, NH₂ Aib), 8.42 (1H, s, H triazole),9.01 (1H, d, J=8.0, NH Trp), 10.81 (1H, s, NH indole), 10.90 (1H, s, NHindole).

(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 96)

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.20 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 3.32 (3H, d,N—CH₃), 3.30-3.45 (2H, m, CH₂β Trp), 4.22 (2H, s, —CH₂—In), 5.30 (1H, m,CHα Trp), 6.91 (1H, t, J=7.5, Hg indole), 6.94 (1H, d, J=7.5, H₅indole), 7.02 (1H, t, J=7.9, He indole), 7.05 (1H, t, J=7.9, H₆ indole),7.08 (1H, d, J=1.9, H₂ indole), 7.12 (1H, d, J=1.9, H₂ indole), 7.29(1H, d, J=8.1, H₇ indole), 7.33 (1H, d, J=8.2, H₇ indole), 7.48 (1H, d,J=7.9, H₄ indole), 7.57 (1H, d, J=7.9H₄ indole), 8.00 (2H, brs, NH₂Aib), 8.85 (1H, d, J=8.2, NH Trp), 10.82 (1H, s, NH indole), 10.98 (1H,s, NH indole).

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 97)

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.30 (3H, s, CH₃ Aib), 1.40 (3H, s, CH₃ Aib), 3.00-3.20 (4H, m,—CH₂ —CH₂ —In), 3.36 (3H, s, N—CH₃), 3.45-3.50 (2H, m, CH₂β Trp), 5.30(1H, m, CHα Trp), 6.95-7.04 (2H, t, H₅ indole), 7.06-7.13 (2H, m, H₆indole), 7.18 (2H, brs, H₂ indole), 7.34 (1H, d, J=8.0, H₇ indole), 7.36(1H, d, J=8.0, H₇ indole), 7.48 (1H, d, J=7.8, H₄ indole), 7.58 (1H, d,J=7.8, H₄ indole), 8.10 (2H, brs, NH₂ Aib), 8.95 (1H, d, J=8.1, NH Trp),10.95 (1H, s, NH indole), 10.96 (1H, s, NH indole).

¹³C NMR (100 MHz,DMSO-d⁶):

δ(ppm) 22.9-25.9 (—CH₂—CH₂-indole), 24.1 (CH₃ Aib), 24.3 (CH₃ Aib), 28.8(CH₂β Trp), 30.7 (—NCH₃), 46.2 (CHα Trp), 57.2 (Cq Aib), 110.2 (C₃indole), 112.3 (2C₇ indole), 113.5 (C₃ indole), 118.9-119.2 (2C₅, 2C₄indole), 121.9 (2C₆ indole), 123.6 (C₂ indole), 125.3 (C₂ indole), 127.7(C₉ indole), 128.0 (C₉ indole), 136.9 (C₈ indole), 137.1 (C₈ indole),155.3 (Cq triazole), 155.8 (Cq triazole), 172.2 (CO Aib).

(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 98)

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.31 (3H, s, CH₃ Aib), 1.42 (3H, s, CH₃ Aib), 3.19 (1H, dd,J=14.5, J=9.6, 1H CH₂ βTrp), 3.35 (1H, dd, J=14.5, J=5.3, 1H C₂ βTrp),4.15 (2H, s, CH₂ indole), 5.26 (1H, m, CαH Trp), 6.95 (1H, t, H₅ Trp),6.96 (1H, t, H₅ indole), 7.05 (1H, t, H₆ Trp), 7.06 (1H, s, H₂ Trp),7.07 (1H, t, H₆ indole), 7.21 (1H, s, H₂ indole), 7.32 (1H, d, H₇ Trp),7.37 (1H, d, H₇ indole), 7.51 (1H, d, J=7.8, H₄ indole), 7.58 (1H, d,J=7.8, H₄ Trp), 8.00 (2H, s, NH₂ Aib), 8.64 (1H, d, J=8.7, NH Trp),10.77 (1H, s, NH indole Trp), 10.92 (1H, s, NH indole).

¹³C NMR (400 MHz,DMSO-d⁶):

δ(ppm) 22.9 (CH₂ indole), 23.2 (CH₃ Aib), 23.3 (CH₃ Aib), 29.4 (Cβ Trp),48.3 (Cα Trp), 56.3 (Cq Aib), 109.7 (C₃ indole), 110.3 (C₃ Trp), 111.2(C₇ Trp), 111.3 (C₇ indole), 118.1 (C₄ Trp, C₅ Trp), 118.3 (C₄ indole),118.4 (C₅ indole), 120.7 (C₆ Trp), 121.0 (C₆ indole), 123.4 (C₂ indole),123.6 (C₂ Trp), 126.8 (C₉ indole), 127.1 (C₉ Trp), 136.0 (C₈ Trp), 136.2(C₈ indole), 157.5 (Cq triazole), 161.7 (Cq triazole), 170.8 (CO Aib).

(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 99)

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 3.25 (1H, dd,J=14.3, J=5.6, 1H CH₂ βTrp), 3.38 (1H, dd, J=14.3, J=9.1, 1H C₂ βTrp),3.68 (3H, s, OCH₃), 3.72 (3H, s, OCH₃), 4.10 (1H, d, J=16.5, 1H C₂indole), 4.16 (1H, d, J=16.5, 1H C₂ indole), 4.96 (1H, d, J=16.8, 1H C₂o,p-dimethoxybenzyl), 5.12 (1H, d, J=16.8, 1H C₂ o,p-dimethoxybenzyl),5.16 (1H, m, CαH Trp), 6.21 (1H, dd, J=8.5, J=2.1, H₅o,p-dimethoxybenzyl), 6.27 (1H, d, J=8.5, H₆ o,p-dimethoxybenzyl), 6.57(1H, d, J=2.1, H₃ o,p-dimethoxybenzyl), 6.83 (1H, t, H₅ Trp), 6.94 (1H,t, H₅ indole), 7.02 (1H, t, H₆ Trp), 7.05 (1H, t, H₂ indole), 7.06 (1H,t, H₆ indole), 7.07 (1H, s, H₂ Trp), 7.07 (1H, t, H₄ Trp), 7.31 (1H, d,H₇ Trp), 7.33 (1H, d, H₇ indole), 7.36 (1H, d, J=7.8, H₄ indole), 8.00(2H, br s, NH₂ Aib), 8.92 (1H, d, J=8.2, NH Trp), 10.79 (1H, s, NHindole Trp), 10.89 (1H, s, NH indole).

¹³C NMR (400 MHz,DMSO-d⁶):

δ(ppm) 21.2 (CH₂indole), 23.1 (CH₃ Aib), 23.2 (CH₃ Aib), 28.6 (Cβ Trp),41.4 (N—CH₂ o,p-dimethoxybenzyl), 45.1 (Cα Trp), 55.2 (OCH₃), 55.4(OCH₃), 56.2 (Cq Aib), 98.5 (C₃ o,p-dimethoxybenzyl), 104.6 (C₅o,p-dimethoxybenzyl), 107.9 (C₃ indole), 109.5 (C₃ Trp), 111.2 (C₇ Trp),111.3 (C₇ indole), 115.1 (C₁ o,p-dimethoxybenzyl), 117.8 (C₄ Trp), 118.1(C₅ Trp), 118.3 (C₄ indole), 118.4 (C₅ indole), 120.8 (C₆ Trp), 121.1(C₆ indole), 123.5 (C₂ indole), 124.3 (C₂ Trp), 126.6 (C₉ indole), 126.8(C₉ Trp), 127.2 (C₆ o,p-dimethoxybenzyl), 136.0 (C₈ Trp), 136.2 (C₈indole), 157.5 (Cq triazole), 154.9 (Cq triazole), 157.2 (C₂o,p-dimethoxybenzyl), 160.3 (C₄ o,p-dimethoxybenzyl), 171.2 (CO Aib).

(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 101)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.22 (3H, s, CH₃ Aib), 1.25 (3H, s, CH₃ Aib), 3.22 (1H, dd, J=14Hz and 6 Hz, CH₂ βTrp), 3.34 (1H, dd, J=14 Hz and 9 Hz, CH₂ βTrp), 3.68(3H, s, OCH₃), 4.11 (2H, m, CH ₂-indole), 5.09 (3H, m, CH αTrp and CH₂-p-methoxybenzyl), 6.70 (4H, s, CHar p-methoxybenzyl), 6.78 (2H, m, H₅indole and H₅ Trp), 6.93 (2H, m, H₆ indole and H₆ Trp), 7.01-7.06 (3H,m, H₂ indole, H₂ and H₄ Trp), 7.31 (3H, m, H₄ and H₇ indole, H₇ Trp),7.98 (3H, brs, NH₂ Aib), 8.92 (1H, d, J=8 Hz, NH amide), 10.77 (1H, s,NH indole), 10.89 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 21.7 (CH₂-indole), 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 28.9 (CH₂βTrp), 45.6 (CH αTrp), 45.8 (CH₂— p-methoxybenzyl), 55.5 (OCH₃), 56.7(Cq Aib), 108.1 (C₃ indole), 109.7 (C₃ Trp), 111.7 (C₇ Trp), 111.9 (C₇indole), 114.5 (C₃ and C₅ p-methoxybenzyl), 118.3 (C₄ Trp), 118.7 (C₄indole), 118.8 (C₅ indole), 118.9 (C₅ Trp), 121.3 (C₆ indole), 121.6 (C₆Trp), 124.2 (C₂ indole), 125.3 (C₂ Trp), 127.1 (C₉ indole), 127.2 (C₉Trp), 127.6 (C₁ p-methoxybenzyl), 127.8 (C₂ and C₆ p-methoxybenzyl),136.4 (C₈ Trp), 136.7 (C₈ indole), 154.2 (Cq triazole), 155.2 (Cqtriazole), 159.2 (C₄ p-methoxybenzyl), 171.9 (CO Aib).

(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 102)

¹H NMR (400 MHz, DMSO-d⁶):

δ(ppm) 1.30 (3H, s, CH₃ Aib), 1.33 (3H, s, CH₃ Aib), 3.26 (1H, dd,J=14.2, J=5.9, 1H CH₂ βTrp), 3.38 (1H, dd, J=14.2, J=8.7, 1H C₂ βTrp),3.69 (3H, s, OCH₃), 3.72 (3H, s, OCH₃), 4.02 (2H, s, CH₂ benzyl), 4.87(1H, d, J=16.7, 1H C₂ o,p-dimethoxybenzyl), 5.08 (1H, d, J=16.7, 1H C₂o,p-dimethoxybenzyl), 5.17 (1H, m, CαH Trp), 6.24 (1H, dd, J=8.4, J=1.7,H₅ o,p-dimethoxybenzyl), 6.28 (1H, d, J=8.4, H₆ o,p-dimethoxybenzyl),6.56 (1H, d, J=1.7, H₃ o,p-dimethoxybenzyl), 6.85 (1H, t, J=7.5, H₅Trp), 7.02 (1H, t, H₆ Trp), 7.07 (2H, m, H₂, H₆ benzyl), 7.08 (1H, s, H₂Trp), 7.09 (1H, d, H₄ Trp), 7.16-7.29 (3H, m, H₃, H₄, H₅ benzyl), 7.31(1H, d, J=8.2, H₇ Trp), 8.01 (2H, s, NH₂ Aib), 8.92 (1H, d, J=7.9, NHTrp), 11.79 (1H, s, NH indole Trp).

¹³C NMR (400 MHz,DMSO-d⁶):

δ(ppm) 23.2 (2CH₃ Aib), 28.7 (Cβ Trp), 30.2 (CH₂-benzyl), 41.3 (CH₂—o,p-dimethoxybenzyl), 45.2 (Cα Trp), 55.2 (OCH₃), 55.4 (OCH₃), 56.2 (CqAib), 98.5 (C₃ o,p-dimethoxybenzyl), 104.7 (C₅ o,p-dimethoxybenzyl),109.$ (C₃ Trp), 111.3 (C₇ Trp), 115.1 (C₁ o,p-dimethoxybenzyl), 117.8(C₄ Trp), 118.2 (C₅ Trp), 120.8 (C₆ Trp), 124.3 (C₂ Trp), 126.5 (C₂, C₆benzyl), 126.8 (C₉ Trp), 127.3 (C₆ o,p-dimethoxybenzyl), 128.3 (C₃, C₄,C₅ Benzyl), 135.8 (C₁ benzyl), 136.0 (C₈ Trp), 153.4 (Cq triazole),155.0 (Cq triazole), 157.2 (C₂ o,p-dimethoxybenzyl), 160.3 (C₄o,p-dimethoxybenzyl), 171.3 (CO Aib).

(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 104)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 2.39-2.53 (4H, m,CH ₂—CH ₂-phenyl), 3.74 (1H, m, CH₂ βTrp), 3.92 (1H, m, CH₂ βTrp), 3.99(2H, s, CH₂-indole), 5.21 (1H, m, CH αTrp), 6.74 (2H, m, H₅ indole andH₅ Trp), 6.90 (1H, t, J_(o)=8 Hz, H₆ Trp), 6.92 (1H, t, J_(o)=8 Hz, H₆indole), 7.01-7.06 (4H, m, H₂ and H₆ phenyl, H₂ indole and H₂ Trp), 7.16(3H, m, H₃, H₄ and H₅ phenyl), 7.27 (1H, d, J_(o)=8 Hz, H₄ Trp), 7.32(1H, d, J_(o)=8 Hz, H₇ Trp), 7.36 (1H, d, J_(o)=8 Hz, H₇ indole), 7.50(1H, d, J_(o)=8 Hz, H₄ indole), 7.99 (3H, brs, NH₂ Aib), 9.02 (1H, s,J=8 Hz, NH amide), 10.79 (1H, s, NH indole Trp), 10.94 (1H, s, NHindole).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 21.4 (CH₂-indole), 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 29.5 (CH₂βTrp), 35.8 (CH₂—CH₂-phenyl), 44.5 (CH₂—CH₂-phenyl), 45.8 (CH αTrp),56.7 (Cq Aib), 108.5 (C₃ indole), 109.9 (C₃ Trp), 114.0 (C₇ indole andC₇ Trp), 118.4 (C₄ Trp), 118.8 (C₄ indole and C₅ Trp), 119.0 (C₅indole), 121.4 (C₆ Trp), 121.7 (C₆ indole), 124.0 (C₂ indole and C₂Trp), 127.1 (C₄ phenyl), 127.7 (C₉ indole and C₉ Trp), 128.8 (C₂ and C₆phenyl), 129.1 (C₃ and C₅ phenyl), 136.5 (C₈ Trp), 136.6 (C₈ indole),137.5 (C₁ phenyl), 153.6 (Cq triazole), 155.0 (Cq triazole), 171.8 (COAib).

(R)—N-(1-(5-benzyl-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 106)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.29 (3H, s, CH₃ Aib), 1.34 (3H, s, CH₃ Aib), 3.37 (4H, m, CH₂βTrp and CH₂-benzyl), 3.74 (1H, t, J=7 Hz, CH₂—CH(Phe)₂), 4.21 (1H, dd,J=14 Hz and 8 Hz, CH ₂—CH(Phe)₂), 4.51 (1H, dd, J=14 Hz and 8 Hz, CH₂—CH(Phe)₂), 5.08 (1H, m, CH αTrp), 6.72 (2H, m, H₂ and H₆ benzyl),6.86-6.93 (5H, m, H₃, H₄ and H₅ benzyl, H₅ and H₆ Trp), 7.03 (1H, s, H₂Trp), 7.06-7.25 (CHar phenyl from CH(Phe)₂), 7.33 (1H, d, J_(o)=8 Hz, H₄Trp), 7.47 (1H, d, J_(o)=8 Hz, H₇ indole), 8.10 (3H, brs, NH₂ Aib), 8.98(1H, d, J=8 Hz, NH amide), 10.94 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 29.4 (CH₂ βTrp), 30.1(CH₂-benzyl), 46.0 (CH αTrp), 47.7 (CH₂—CH(Phe)₂), 51.3 (CH(Phe)₂), 56.8(Cq Aib), 109.8 (C₃ Trp), 112.0 (C₇ Trp), 118.5 (C₄ Trp), 119.0 (C₅Trp), 121.5 (C₆ Trp), 124.8 (C₂ Trp), 127.1 (C₄ phenyl from CH(Phe)₂),127.4 (C₉ Trp, C₂ and C₆ benzyl), 128.3 (C₂ and C₆ phenyl fromCH(Phe)₂), 128.8-129.1 (C₃ and C₅ phenyl from CH(Phe)₂, C₃, C₄ and C₅benzyl), 136.2 (C₁ benzyl), 136.5 (C₈ Trp), 141.0 (C₁ phenyl fromCH(Phe)₂), 153.5 (Cq triazole), 155.1 (Cq triazole), 172.0 (CO Aib)

(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 107)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.34 (3H, s, CH₃ Aib), 1.38 (3H, s, CH₃ Aib), 2.06 (1H, m, CH₂—CH₂-indole), 2.30 (1H, m, CH₂—CH ₂-indole), 2.78 (2H, m, CH ₂—CH₂-indole),3.35 (1H, dd, J=14 Hz and 7 Hz, CH₂ βTrp), 3.46 (1H, dd, J=14 Hz and 9Hz, CH₂ βTrp), 3.58 (1H, t, J=7 Hz, CH₂—CH(Phe)₂), 4.14 (1H, dd, J=14 Hzand 8 Hz, CH ₂—CH(Phe)₂), 4.39 (1H, dd, J=14 Hz and 7 Hz, CH₂—CH(Phe)₂), 5.12 (1H, m, CH αTrp), 6.50 (2H, m, H₅ indole and H₅ Trp),6.76 (2H, m, H₆ indole and H₆ Trp), 6.87 (2H, m, H₂ indole and H₂ Trp),6.89-6.96 (2H, m, H₄ phenyl), 7.03-7.15 (8H, m, H₂, H₃, H₅ and H₆phenyl), 7.33 (3H, m, H₄ indole, H₄ and H₇ Trp), 7.47 (1H, d, J=8 Hz, H₇indole), 8.11 (3H, brs, NH₂ Aib), 9.04 (1H, d, J=8 Hz, NH amide), 10.76(1H, s, NH indole), 10.96 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 22.4 (CH₂—CH₂-indole), 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 24.9(CH₂—CH₂-indole), 29.6 (CH₂ βTrp), 46.1 (CH αTrp), 47.5 (CH₂—CH(Phe)₂),51.5 (CH₂—CH(Phe)₂), 56.8 (Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp),112.1 (C₇ indole), 113.5 (C₃ indole), 118.4 (C₄ Trp), 118.7 (C₄ and C₅indole), 119.0 (C₅ Trp), 121.4 (C₆ indole and C₆ Trp), 122.8 (C₂indole), 125.0 (C₂ Trp), 127.2 (C₉ indole and C₉ Trp), 127.3 (C₄phenyl), 128.2 (C₂ and C₆ phenyl), 128.7 (C₃ and C₅ phenyl), 136.6 (C₈indole and C₈ Trp), 141.0 (C₁ phenyl), 154.6 (2 Cq triazole), 172.0 (COAib).

(R)—N-(1-(4,5-dibenzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 109)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.23 (3H, s, CH₃ Aib), 1.26 (3H, s, CH₃ Aib), 3.23 (1H, dd, J=14Hz and 6 Hz, CH₂ βTrp), 3.35 (1H, dd, J=14 Hz and 9 Hz, CH₂ βTrp), 3.99(2H, s, C—CH ₂-phenyl), 5.10 (3H, m, N—CH ₂-phenyl and CH αTrp), 6.77(3H, m, H₅ Trp, H₂ and H₆ phenyl from N—CH₂-phenyl), 6.99 (2H, m, H₂ andH₆ Trp), 7.01-7.07 (3H, m, H₄ Trp, H₂ and H₆ from C—CH₂-phenyl),7.15-7.23 (6H, m, H₃, H₄ and H₅ phenyl from N—CH₂-phenyl and fromC—CH₂-phenyl), 7.25 (1H, d, J=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib),8.91 (1H, d, J=8 Hz, NH amide), 10.78 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 29.0 (CH₂ βTrp), 30.6(C—CH₂-phenyl), 45.7 (CH αTrp), 46.1 (N—CH₂-phenyl), 56.7 (Cq Aib),109.8 (C₃ Trp), 111.7 (C₇ Trp), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.2(C₆ Trp), 124.8 (C₂ Trp), 126.3 (C₂ and C₆ phenyl from N—CH₂-phenyl),127.0 (C₂ and C₆ phenyl from C—CH₂-phenyl), 127.2 (C₉ Trp), 128.0 (C₄phenyl from N—CH₂-phenyl), 128.8 (C₃, C₄ and C₅ phenyl fromC—CH₂-phenyl), 128.9 (C₃ and C₅ phenyl from N—CH₂-phenyl), 135.8 (C₁phenyl from N—CH₂-phenyl), 136.2 (C₁ phenyl from C—CH₂-phenyl), 136.4(C₈ Trp), 153.9 (Cq triazole), 155.3 (Cq triazole), 171.9 (CO Aib).

(R)—N-(1-(5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 110)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 0.71 (3H, t, ³J=7 Hz, (CH₂)₅—CH ₃), 0.87 (4H, m, 2 CH₂), 0.95(2H, m, CH ₂—CH₃), 1.00 (2H, m, N—CH₂—CH ₂), 1.36 (6H, s, CH₃ Aib), 3.36(1H, dd, ³J=14 Hz and 7 Hz, CH₂ βTrp), 3.41 (1H, dd, ³J=14 Hz and 7 Hz,CH₂ βTrp), 3.50 (1H, m, N—CH ₂), 3.65 (1H, m, N—CH ₂), 4.11 (2H, s, CH₂-benzyl), 5.14 (1H, m, CH αTrp), 6.90 (1H, t, J_(o)=7 Hz, H₅ Trp), 7.01(1H, t, J_(o)=7 Hz, H₆ Trp), 7.04 (1H, s, H₂ Trp), 7.09 (2H, m, H₂ andH₆ benzyl), 7.17-7.29 (4H, m, H₄ Trp, H₃, H₄ and H₅ benzyl), 7.47 (1H,d, J_(o)=8 Hz, H₇ Trp), 8.10 (3H, brs, NH₂ Aib), 9.05 (1H, d, J=7 Hz, NHamide), 10.84 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 14.1 ((CH₂)₅—CH₃), 22.1 (CH₂—CH₃), 23.8 (CH₃ Aib), 23.5 (CH₃Aib), 25.8 (CH₃—CH₂—CH₂—CH₂), 29.5 (CH₂ βTrp), 30.3 (N—CH₂—CH₂), 30.8(CH₂-benzyl and CH₃—CH₂—CH₂), 43.3 (N—CH₂—CH₂), 46.1 (CH αTrp), 56.8 (CqAib), 109.6 (C₃ Trp), 111.9 (C₇ Trp), 118.2 (C₄ Trp), 118.8 (C₅ Trp),121.4 (C₆ Trp), 124.7 (C₂ Trp), 127.2 (C₂ and C₆ benzyl), 127.3 (C₉Trp), 128.8 (C₃, C₄ and C₅ benzyl), 136.2 (C₁ benzyl), 136.5 (C₈ Trp),153.1 (Cq triazole), 155.1 (Cq triazole), 171.9 (CO Aib).

(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 111)

¹H NMR (400 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.31 (3H, s, CH₃ Aib), 1.35 (3H, s, CH₃ Aib), 2.51 (2H, m, CH₂—CH₂-indole), 3.37 (2H, m, CH₂ βTrp), 3.76-3.90 (4H, m, CH ₉-benzyl and CH₂—CH₂-indole), 5.25 (1H, m, CH αTrp), 6.88 (2H, t, J_(o)=7 hz, H₅ indoleand H₅ Trp), 6.95 (2H, t, J_(o)=7 Hz, H₆ indole and H₆ Trp), 7.03 (4H,m, H₂ Trp, H₂ indole, H₂ and H₆ benzyl), 7.16 (2H, d, J_(o)=8 Hz, H₄indole and H₄ Trp), 7.20-7.30 (4H, 3, H₇ indole, H₃, H₄ and H₅ benzyl),7.47 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.05 (3H, brs, NH₂ Aib), 9.05 (1H, d,J=8 Hz, NH amide), 10.83 (1H, s, NH indole), 10.88 (1H, s, NH indoleTrp).

¹³C NMR (100 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 29.6 (CH₂ βTrp), 30.3 (CH₂-benzyland CH₂-CH₂-indole), 44.1 (CH₂—CH₂-indole), 46.1 (CH αTrp), 56.8 (CqAib), 109.8 (C₃ Trp), 109.9 (C₃ indole), 111.9 (C₇ indole and C₇ Trp),118.3 (C₄ Trp), 118.4 (C₄ indole), 118.9 (C₅ indole and C₅ Trp), 121.3(C₆ Trp), 121.5 (C₆ indole), 123.7 (C₂ indole), 124.7 (C₂ Trp), 127.0(C₉ indole), 127.2 (C₂ and C₆ benzyl), 127.4 (C₉ Trp), 128.8 (C₃ and C₅benzyl), 129.0 (C₄ benzyl), 136.3 (C₁ benzyl), 136.4 (C₈ indole and C₈Trp), 153.1 (Cq triazole), 155.3 (Cq triazole), 171.8 (CO Aib).

(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 112)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.26 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 3.24 (1H, dd, J=14Hz and 6 Hz, CH₂ βTrp), 3.33 (1H, dd, J=14 Hz and 9 Hz, CH₂ βTrp), 3.64(3H, s, OCH₃), 3.68 (3H, s, OCH₃), 3.99 (2H, s, CH₂ phenyl), 4.84 (1H,d, J=17 Hz, CH₂-o,p-dimethoxybenzyl), 5.05 (1H, d, J=17 Hz,CH₂-o,p-dimethoxybenzyl), 5.13 (1H, m, CH αTrp), 6.24 (2H, m, H₅ and H₆o,p-dimethoxybenzyl), 6.52 (1H, d, J_(m)=2 Hz, H₃ o,p-dimethoxybenzyl),6.83 (1H, t, J_(o)=7 Hz, H₅ Trp), 7.01 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.04(1H, s, H₂ Trp), 7.05-7.23 (6H, m, H₄ Trp and CHar phenyl), 7.27 (1H, d,J_(o)=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.90 (1H, d, J=8 Hz, NHamide), 10.77 (1H, d, J=2 Hz, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 29.1 (CH₂ βTrp), 30.6 (CH₂-phenyl), 41.9(CH₂-o,p-dimethoxybenzyl), 45.7 (CH αTrp), 55.7 (OCH₃), 55.9 (OCH₃),56.7 (Cq Aib), 99.9 (C₃ o,p-dimethoxybenzyl), 105.1 (C₅o,p-dimethoxybenzyl), 109.9 (C₃ Trp), 111.7 (C₇ Trp), 115.5 (C₁o,p-dimethoxybenzyl), 118.3 (C₄ Trp), 118.6 (C₅ Trp), 121.3 (C₆ Trp),124.2 (C₂ Trp), 127.0 (C₆ o,p-dimethoxybenzyl), 127.3 (C₉ Trp), 127.8(C₄ phenyl), 128.8 (C₂, C₃, C₅ and C₆ phenyl), 136.2 (C₈ Trp), 136.4 (C₁phenyl), 153.9 (Cq triazole), 155.5 (Cq triazole), 157.6 (C₂o,p-dimethoxybenzyl), 160.8 (C₄ o,p-dimethoxybenzyl), 171.8 (CO amide).

(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 113)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.24 (3H, s, CH₃ Aib), 1.27 (3H, s, CH₃ Aib), 2.83 (4H, s, CH₂—CH ₂-phenyl), 3.32 (2H, m, CH₂ βTrp), 3.61 (6H, s, OCH₃), 5.02 (2H, m,CH₂-m-dimethoxybenzyl), 5.18 (1H, m, CH αTrp), 6.07 (2H, d, J_(m)=2 Hz,H₂ and H₆ m-dimethoxybenzyl), 6.42 (1H, brs, H₄ m-dimethoxybenzyl), 6.83(1H, t, J_(o)=7 Hz, H₅ Trp), 6.99 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.08 (1H,d, J=2 Hz, H₂ Trp), 7.13 (3H, t, J_(o)=8 Hz, H₃, H₄ and H₅ phenyl), 7.20(3H, d, J_(o)=7 Hz, H₂ and H₆ phenyl, H₄ Trp), 7.28 (1H, d, J_(o)=8 Hz,H₇ Trp), 7.99 (3H, brs, NH₂ Aib), 8.92 (1H, d, J=8 Hz, NH amide), 10.77(1H, s, NH indole).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.5 (CH₂—CH₂-phenyl), 29.2 (CH₂βTrp), 32.7 (CH₂—CH₂-phenyl), 45.6 (CH αTrp), 45.8 (CH₂—m-dimethoxybenzyl), 55.6 (OCH₃), 56.8 (Cq Aib), 99.6 (C₄m-dimethoxybenzyl), 104.6 (C₂ and C₆ m-dimethoxybenzyl), 109.9 (C₃ Trp),111.8 (C₇ Trp), 118.2 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.8(C₂ Trp), 126.5 (C₄ phenyl), 127.3 (C₉ Trp), 128.7 (C₂, C₃, C₅ and C₆phenyl), 136.4 (C₈ Trp), 138.6 (C₄ m-dimethoxybenzyl), 140.9 (C₁phenyl), 154.6 (Cq triazole), 154.8 (Cq triazole), 161.4 (C₃ and C₅m-dimethoxybenzyl), 171.8 (CO amide).

(R)—N-(1-(4-(4-bromobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 114)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm)1.23 (3H, s, CH₃ Aib), 1.25 (3H, s, CH₃ Aib), 3.26 (1H, dd, ³J=14Hz and 6 Hz, CH₂ Trp), 3.34 (1H, dd, ³J=14 Hz and 9 Hz, CH₂ βTrp), 4.01(2H, m, CH₂-benzyl), 5.01 (1H, m, CH αTrp), 5.08 (2H, s,CH₂-p-bromobenzyl), 6.59 (2H, d, J_(o)=8 Hz, H₂ and H₆ p-bromobenzyl),6.81 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.94 (1H, s, H₂ Trp), 6.98 (1H, t,J_(o)=7 Hz, H₆ Trp), 7.06 (2H, m, H₂ and H₆ benzyl), 7.12 (1H, d,J_(o)=7 Hz, H₄ Trp), 7.16-7.20 (3H, m, H₃, H₄ and H₅ benzyl), 7.26 (1H,d, J_(o)=8 Hz, H₇ Trp), 7.29 (2H, d, J_(o)=8 Hz, H₃ and H₅ benzyl), 8.00(3H, brs, NH₂ Aib), 8.92 (1H, d, J=8 Hz, NH amide), 10.78 (1H, s, NHindole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 29.0 (CH₂ β Trp), 30.5(CH₂-benzyl), 45.6 (CH₂ -p-bromobenzyl), 45.7 (CH α Trp), 56.7 (Cq Aib),109.7 (C₃ Trp), 111.8 (C₇ Trp), 118.2 (C₄ tryptophae), 118.7 (C₅ Trp),121.2 (C₄ p-bromobenzyl), 121.3 (C₆ Trp), 124.9 (C₂ typtophane), 127.0(C₂ and C₆ benzyl), 127.2 (C₉ Trp), 128.4 (C₂ and C₆ p-bromobenzyl),128.9 (C₃, C₄ and C₅ benzyl), 131.9 (C₃ and C₅ p-bromobenzyl), 135.2 (C₁p-bromobenzyl), 136.2 (C₈ Trp), 136.4 (C₁ benzyl), 153.9 (Cq triazole),155.3 (Cq triazole), 171.9 (CO Aib).

(R)—N-(1-(4-(2-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 115)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.24 (3H, s, CH₃ Aib), 1.27 (3H, s, CH₃ Aib), 3.20 (1H, dd, J=14Hz and 5 Hz, CH₂ βTrp), 3.33 (1H, dd, J=14 Hz and 9 Hz, CH₂ βTrp), 3.68(3H, s, OCH₃), 4.00 (2H, s, CH₂-phenyl), 4.95 (1H, d, J=17 Hz,CH₂-o-methoxybenzyl), 5.07 (1H, m, CH αTrp), 5.18 (1H, d, J=17 Hz,CH₂-o-methoxybenzyl), 6.27 (1H, d, J_(o)=8 Hz, H₃ o-methoxybenzyl), 6.67(1H, t, J_(o)=7 Hz, H₅ Trp), 6.77 (1H, t, J_(o)=6 Hz, H₆ Trp), 6.92-7.05(6H, m, H₂ Trp, H₂ and H₆ phenyl, H₄, H₅ and H₆ o-methoxybenzyl),7.14-7.26 (5H, m, H₄ and H₇ Trp, H₃, H₄ and H₅ phenyl), 8.03 (3H, brs,NH₂ Aib), 8.91 (1H, d, J=8 Hz, NH amide), 10.78 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.6 (CH₃ Aib), 29.1 (CH₂ β Trp), 30.5(CH₂-phenyl), 42.1 (CH₂-o-methoxybenzyl), 45.7 (CH α Trp), 55.9 (OCH₃),56.7 (Cq Aib), 109.8 (C₃ Trp), 111.3 (C₃ o-methoxybenzyl), 111.7 (C₇Trp), 118.2 (C₄ Trp), 118.7 (C₅ Trp), 120.9 (C₅ o-methoxybenzyl), 121.2(C₆ Trp), 123.3 (C₁ o-methoxybenzyl), 124.8 (C₂ Trp), 126.6 (C₂ and C₆phenyl), 127.1 (C₄ o-methoxybenzyl), 127.2 (C₉ Trp), 128.8 (C₃, C₄ andC₅ phenyl), 129.5 (C₆ o-methoxybenzyl), 136.0 (C₁ phenyl), 136.4 (C₈Trp), 154.0 (Cq triazole), 155.6 (Cq triazole), 156.5 (C₂o-methoxybenzyl), 171.8 (CO Aib).

(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 116)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.28 (3H, s, CH₃ Aib), 1.32 (3H, s, CH₃ Aib), 2.81 (4H, m, CH₂—CH ₂-phenyl), 3.30 (2H, t, CH₂ βTrp), 3.61 (3H, s, OCH₃), 3.69 (3H, s,OCH₃), 4.87 (1H, d, J=17 Hz, CH₂-o,p-dimethoxybenzyl), 5.03 (1H, d, J=17Hz, CH₂-o,p-dimethoxybenzyl), 5.20 (1H, m, CH αTrp), 6.29 (1H, dd,J_(o)=8 Hz and J_(m)=2 Hz, H₅ o,p-dimethoxybenzyl), 6.43 (1H, d, J_(o)=8Hz, H₆ o,p-dimethoxybenzyl), 6.55 (1H, d, J_(m)=2 Hz, H₃o,p-dimethoxybenzyl), 6.83 (1H, t, J_(o)=8 Hz, H₅ Trp), 6.99 (1H, t,J_(o)=8 Hz, H₆ Trp), 7.06 (1H, d, J=2 Hz, H₂ Trp), 7.09-7.25 (6H, m, H₄Trp and CHar phenyl), 7.28 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.04 (3H, brs,NH₂ Aib), 8.92 (1H, d, J=8 Hz, NH amide), 10.79 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.7 (CH₃ Aib), 26.5 (CH₂—CH₂-phenyl), 29.1 (CH₂βTrp), 32.7 (CH₂—CH₂-phenyl), 41.8 (CH₂-o,p-dimethoxybenzyl), 45.7 (CHαTrp), 55.7 (OCH₃), 55.9 (OCH₃), 56.8 (Cq Aib), 99.1 (C₃o,p-dimethoxybenzyl), 105.2 (C₅ o,p-dimethoxybenzyl), 109.9 (C₃ Trp),111.8 (C₇ Trp), 115.6 (C₁ o,p-dimethoxybenzyl), 118.3 (C₄ Trp), 118.7(C₅ Trp), 121.3 (C₆ Trp), 124.4 (C₂ Trp), 126.6 (C₄ phenyl), 127.3 (C₉Trp), 128.2 (C₆ o,p-dimethoxybenzyl), 128.7 (C₂, C₃, C₅ and C₆ phenyl),136.4 (C₈ Trp), 140.9 (C₁ phenyl), 154.6 (Cq triazole), 155.0 (Cqtriazole), 157.8 (C₂ o,p-dimethoxybenzyl), 160.9 (C₄o,p-dimethoxybenzyl), 171.8 (CO Aib).

(R)—N-(1-(4,5-diphenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 117)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.32 (3H, s, CH₃ Aib), 1.37 (3H, s, CH₃ Aib), 2.59 (4H, m, C—CH₂—CH ₂-phenyl), 2.83 (2H, t, J=8 Hz, N—CH₂—CH ₂-phenyl), 3.38 (2H, m,N—CH ₂—CH₂-phenyl), 3.84 (1H, m, CH₂ βTrp), 3.94 (1H, m, CH₂ βTrp), 5.23(1H, m, CH αTrp), 6.84 (2H, m, H₄ phenyl from C—CH₂—CH₂-phenyl and H₄phenyl from N—CH₂—CH₂-phenyl), 6.93 (1H, t, J_(o)=8 Hz, H₅ Trp), 7.00(1H, t, J_(o)=8 Hz, H₆ Trp), 7.07 (1H, d, J=2 Hz, H₂ Trp), 7.11-7.27(9H, m, H₂, H₃, H₅ and H₆ phenyl from C—CH₂—CH₂-phenyl, H₂, H₃, H₅ andH₆ phenyl from N—CH₂—CH₂-phenyl and H₄ Trp), 7.50 (1H, d, J_(o)=8 Hz, H₇Trp), 8.07 (3H, brs, NH₂ Aib), 9.04 (1H, d, J=8 Hz, NH amide), 10.85(1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 25.9 (C—CH₂—CH₂-phenyl), 29.5(CH₂ βTrp), 32.4 (C—CH₂—CH₂-phenyl), 35.8 (N—CH₂—CH₂-phenyl), 44.2(N—CH₂—CH₂-phenyl), 45.9 (CH αTrp), 56.8 (Cq Aib), 109.7 (C₃ Trp), 111.9(C₇ Trp), 118.4 (C₄ Trp), 118.9 (C₅ Trp), 121.4 (C₆ Trp), 124.8 (C₂Trp), 126.6 (C₄ phenyl from C—CH₂—CH₂-phenyl), 127.2 (C₄ phenyl fromN—CH₂—CH₂-phenyl), 127.4 (C₉ Trp), 128.7 (C₂ and C₆ phenyl fromC—CH₂—CH₂-phenyl, C₂ and C₆ phenyl from N—CH₂—CH₂-phenyl), 128.8 (C₃ andC₅ phenyl from C—CH₂—CH₂-phenyl, C₃ and C₅ phenyl fromN—CH₂—CH₂-phenyl), 136.5 (C₁ phenyl from N—CH₂—CH₂-phenyl), 137.5 (C₁phenyl from C—CH₂—CH₂-phenyl), 140.8 (C₈ Trp), 154.1 (Cq triazole),154.7 (Cq triazole), 171.9 (CO Aib).

(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 118)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.24 (3H, s, CH₃ Aib), 1.25 (3H, s, CH₃ Aib), 3.33 (2H, m, CH₂βTrp), 4.04 (2H, s, CH ₂-benzyl), 5.05 (1H, m, CH αTrp), 5.12 (2H, s,CH₂-m,p-dichlorobenzyl), 6.49 (1H, dd, J_(o)=8 Hz and J_(m)=2 Hz, H₆m,p-dichlorobenzyl), 6.80 (1H, t, J_(o)=8 Hz, H₅ Trp), 6.87 (1H, d,J_(m)=2 Hz, H₂ Trp), 6.98 (1H, t, J_(o)=7 Hz, H₆ Trp), 7.02-7.10 (3H, m,H₂ and H₆ benzyl, H₅ m,p-dichlorobenzyl), 7.18 (3H, m, H₃, H₄ and H₅benzyl), 7.26 (2H, m, H₄ and H₇ Trp), 8.04 (3H, brs, NH₂ Aib), 8.94 (1H,d, J=9 Hz, NH amide), 10.81 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.4 (CH₃ Aib), 23.8 (CH₃ Aib), 29.0 (CH₂ βTrp), 30.4(CH₂-benzyl), 45.1 (CH₂-m,p-dichlorobenzyl), 45.6 (CH αTrp), 56.7 (CqAib), 109.6 (C₃ Trp), 111.8 (C₇ Trp), 118.1 (C₄ Trp), 118.6 (C₅ Trp),121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.4 (C₆ m,p-dichlorobenzyl), 127.0 (C₂m,p-dichlorobenzyl), 127.2 (C₉ Trp), 128.4 (C₂ and C₆ benzyl), 130.7 (C₄and C₅ m,p-dichlorobenzyl), 131.8 (C₃ m,p-dichlorobenzyl), 136.0 (C₁benzyl), 136.4 (C₈ Trp), 136.7 (C₁ m,p-dichlorobenzyl), 154.1 (Cqtriazole), 155.2 (Cq triazole), 172.0 (CO Aib).

(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide(Compound 120)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.18 (3H, s, CH₃ Aib), 1.26 (3H, s, CH₃ Aib), 3.09 (1H, dd, J=14Hz and 6 Hz, CH₂ βPhe), 3.18 (1H, dd, J=14 Hz and 9 Hz, CH₂ βPhe), 3.99(2H, d, J=4 Hz, CH₂-phenyl), 4.95 (1H, d, J=16 Hz, CH₂-p-methoxybenzyl),5.06 (1H, d, J=16 Hz, CH₂-p-methoxybenzyl), 5.13 (1H, m, CH αPhe), 6.78(4H, s, CHar p-methoxybenzyl), 7.02-7.08 (4H, m, H₂ and H₆ phenyl, H₂and H₆ Phe), 7.12-7.25 (6H, m, H₃, H₄ and H₅ phenyl, H₃, H₄ and H₅ Phe),7.99 (3H, brs, NH₂ Aib), 8.92 (1H, d, J=8 Hz, NH amide).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.4 (CH₃ Aib), 23.8 (CH₃ Aib), 30.7 (CH₂-phenyl), 38.7 (CH₂βPhe), 45.9 (CH₂-p-methoxybenzyl), 46.4 (CH αPhe), 55.6 (OCH₃), 56.7 (CqAib), 114.6 (C₃ and C₅ p-methoxybenzyl), 126.9 and 127.1 (C₄ phenyl andC₄ Phe), 127.7 (C₁ p-methoxybenzyl), 128.2 (C₂ and C₆ Phe), 128.5 (C₃and C₅ Phe), 128.9 (C₂, C₃, C₅ and C₆ phenyl), 129.7 (C₂ and C₆p-methoxybenzyl), 136.3 (C₁ phenyl), 137.6 (C₁ Phe), 154.0 (Cqtriazole), 154.9 (Cq triazole), 159.2 (C₄ p-methoxybenzyl), 171.7 (COamide).

(R)—N-(1-(4-(4-fluorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 121)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 2.82 (4H, m, CH₂—CH ₂-phenyl), 3.34 (2H, m, CH₂ βTrp), 5.06 (2H, s,CH₂-p-fluorobenzyl), 5.16 (1H, m, CH αTrp), 6.85 (3H, m, H₅ Trp, H₃ andH₅ p-fluorobenzyl), 6.98-7.04 (4H, m, H₂ and H₆ Trp, H₂ and H₆ phenyl),7.09-7.11 (2H, m, H₂ and H₆ p-fluorobenzyl), 7.15 (1H, d, J_(o)=6 Hz, H₄Trp), 7.19 (3H, t, J_(o)=8 Hz, H₃, H₄ and H₅ phenyl), 7.29 (1H, d,J_(o)=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.94 (1H, d, J=8 Hz, NHamide), 10.78 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.5 (CH₂—CH₂-phenyl), 29.2 (CH₂βTrp), 32.7 (CH₂—CH₂-phenyl), 45.4 (CH₂-p-fluorobenzyl), 45.7 (CH αTrp),56.8 (Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 115.9 and 116.2 (C₃ andC₅ p-fluorobenzyl), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp),124.8 (C₂ Trp), 126.5 (C₄ phenyl), 127.3 (C₉ Trp), 128.5 (C₂ and C₆p-fluorobenzyl), 128.7 (C₂, C₃, C₅ and C₆ phenyl), 132.2 (C₁p-fluorobenzyl), 136.4 (C₈ Trp), 140.9 (C₁ phenyl), 154.5 (Cq triazole),154.7 (Cq triazole), 160.3 (C₄ p-fluorobenzyl), 171.9 (CO amide).

NMR ¹⁹F (282 MHz, DMSO-d⁶, 300° K):

δ(ppm)-114.9 (1F, m, p-fluorobenzyl).

(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 122)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.25 (3H, s, CH₃ Aib), 1.26 (3H, s, CH₃ Aib), 2.84 (4H, m, CH₂—CH ₂-phenyl), 3.34 (2H, d, J=7 Hz, CH₂ βTrp), 5.11 (3H, m, CH αTrp andCH₂-m,p-dichlorobenzyl), 6.63 (1H, dd, J_(o)=8 Hz and J_(m)=2 Hz, H₆m,p-dichlorobenzyl), 6.83 (1H, t, J_(o)=8 Hz, H₅ Trp), 6.99 (1H, t,J_(o)=8 Hz, H₆ Trp), 7.05 (1H, d, J=2 Hz, H₂ Trp), 7.12 (5H, m, CHarphenyl), 7.17 (1H, d, J_(o)=8 Hz, H₄ Trp), 7.21 (1H, s, H₂m,p-dichlorobenzyl), 7.27 (1H, d, J_(o)=8 Hz, H₅ m,p-dichlorobenzyl),7.39 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.02 (3H, brs, NH₂ Aib), 8.94 (1H, d,J=8 Hz, NH amide), 10.78 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.4 (CH₂—CH₂-phenyl), 29.1 (CH₂βTrp), 32.6 (CH₂—CH₂-phenyl), 44.7 (CH₂-m,p-dichlorobenzyl), 45.6 (CHαTrp), 56.7 (Cq Aib), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 118.1 (C₄ Trp),118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.5 (C₄ phenyl and C₆m,p-dichlorobenzyl), 127.2 (C₉ Trp), 128.7 (C₂, C₃, C₅ and C₆ phenyl, C₂m,p-dichlorobenzyl), 130.9 (C₄ m,p-dichlorobenzyl), 131.4 (C₅m,p-dichlorobenzyl), 132.0 (C₃ m,p-dichlorobenzyl), 136.4 (C₈ Trp),137.2 (C₁ m,p-dichlorobenzyl), 140.8 (C₁ phenyl), 154.5 (Cq triazole),154.7 (Cq triazole), 171.9 (CO amide).

(R)—N-(1-(4-(4-methylbenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 124)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.22 (3H, s, CH₃ Aib), 1.27 (3H, s, CH₃ Aib), 2.22 (3H, s, CH₃p-methylbenzyl), 3.22 (1H, dd, J=14 Hz and 6 Hz, CH₂ βTrp), 3.33 (1H,dd, J=14 Hz and 9 Hz, CH₂ βTrp), 3.99 (2H, s, CH₂-benzyl), 5.04 (2H, s,CH₂-p-methylbenzyl), 5.09 (1H, m, CH αTrp), 6.64 (2H, d, J_(o)=8 Hz, H₃and H₅ p-methylbenzyl), 6.78 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.98 (4H, t,J_(o)=7 Hz, H₆ Trp, H₃, H₄ and H₅ benzyl), 7.01 (1H, d, J=2 Hz, H₂ Trp),7.07 (2H, d, J_(o)=7 Hz, H₂ and H₆ p-methylbenzyl), 7.20 (3H, m, H₄ Trp,H₂ and H₆ benzyl), 7.26 (1H, d, J_(o)=8 Hz, H₇ Trp), 7.98 (3H, brs, NH₂Aib), 8.89 (1H, d, J=8 Hz, NH amide), 10.74 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 21.0 (CH₃ p-methylbenzyl), 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 29.1(CH₂ βTrp), 30.6 (CH₂-benzyl), 45.7 (CH αTrp), 46.0(CH₂-p-methylbenzyl), 56.7 (Cq Aib), 109.8 (C₃ Trp), 111.7 (C₇ Trp),118.3 (C₄ Trp), 118.6 (C₅ Trp), 121.2 (C₆ Trp), 124.8 (C₂ Trp), 126.3(C₃ and C₅ p-methylbenzyl), 127.0 (C₄ benzyl), 127.2 (C₉ Trp), 128.9(C₂, C₃, C₅ and C₆ benzyl), 129.7 (C₂ and C₆ p-methylbenzyl), 132.9 (C₁p-methylbenzyl), 136.3 (C₄ p-methylbenzyl), 136.4 (C₈ Trp), 137.4 (C₁benzyl), 153.9 (Cq triazole), 155.3 (Cq triazole), 171.8 (CO amide).

(S)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 125)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.31 (3H, s, CH₃ Aib), 1.74 (2H, m,(CH₂—CH ₂—CH₂-phenyl), 2.52 (4H, t, J=7 Hz, CH ₂—CH₂—CH ₂-phenyl), 3.35(2H, d, J=7 Hz, CH₂ βTrp), 3.68 (3H, s, OCH₃), 4.98 (2H, s,CH₂-p-methoxybenzyl), 5.20 (1H, m, CH αTrp), 6.75 (4H, s, CHarp-methoxybenzyl), 6.83 (1H, t, J_(o)=8 Hz, H₅ Trp), 6.99 (1H, t, J_(o)=7Hz, H₆ Trp), 7.06 (3H, m, H₂ and H₆ phenyl, H₂ Trp), 7.14 (1H, d,J_(o)=7 Hz, H₄ Trp), 7.19 (3H, t, J_(o)=8 Hz, H₃, H₄ and H₅ phenyl),7.29 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.94 (1H, d,J=8 Hz, NH amide), 10.79 (1H, d, J=2 Hz, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 24.1 (CH₂—CH₂—CH₂-phenyl), 28.5(CH₂—CH₂—CH₂-phenyl), 29.2 (CH₂ βTrp), 34.7 (CH₂—CH₂—CH₂-phenyl), 45.5(CH₂-p-methoxybenzyl), 45.8 (CH αTrp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.8(C₃ Trp), 111.8 (C₇ Trp), 114.6 (C₃ and C₅ p-methoxybenzyl), 118.3 (C₄Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.2 (C₄ phenyl),127.3 (C₉ Trp), 127.8 (C₁ p-methoxybenzyl), 127.9 (C₃, C₄ and C₅phenyl), 128.7 (C₂ and C₆ p-methoxybenzyl), 136.4 (C₈ Trp), 141.7 (C₁phenyl), 154.7 (Cq triazole), 154.8 (Cq triazole), 159.2 (C₁p-methoxybenzyl), 171.9 (CO amide).

(S)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 126)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.25 (3H, s, CH₃ Aib), 1.28 (3H, s, CH₃ Aib), 3.26 (1H, dd, J=14Hz and 6 Hz, CH₂ βTrp), 3.34 (1H, dd, J=14 Hz and 8 Hz, CH₂ βTrp), 3.99(2H, s, CH₂-phenyl), 4.98 (2H, s, CH₂-p-methoxybenzyl), 5.13 (1H, m, CHαTrp), 6.68 (4H, s, CHar p-methoxybenzyl), 6.80 (1H, t, J_(o)=8 Hz, H₅Trp), 6.99 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.02-7.06 (4H, m, H₂ and H₄ Trp,H₂ and H₆ phenyl), 7.20 (3H, m, H₃, H₄ and H₅ phenyl), 7.27 (1H, d,J_(o)=8 Hz, H₇ Trp), 8.00 (3H, s, NH₂ Aib), 8.91 (1H, d, J=8 Hz, NHamide), 10.76 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 29.1 (CH₂ βTrp), 30.6(CH₂-phenyl), 45.7 (CH αTrp and CH₂-p-methoxybenzyl), 55.5 (OCH₃), 56.7(Cq Aib), 109.8 (C₃ Trp), 111.7 (C₇ Trp), 114.5 (C₃ and C₅p-methoxybenzyl), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.8(C₂ Trp), 127.1 (C₄ phenyl), 127.3 (C₉ Trp), 127.6 (C₁ p-methoxybenzyl),127.8 (C₂ and C₆ p-methoxybenzyl), 128.8 (C₂ and C₆ phenyl), 128.9 (C₃and C₅ phenyl), 136.3 (C₈ Trp), 136.4 (C₁ phenyl), 153.8 (Cq triazole),155.2 (Cq triazole), 159.2 (C₄ p-methoxybenzyl), 171.9 (CO amide).

N—((R)-1-(4-(4-nitrobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 128)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.28 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 2.77-2.94 (4H, m,CH ₂—CH ₂-phenyl), 3.28 (1H, dd, ³J=14 Hz and 8 Hz, CH₂ βTrp), 3.43 (1H,dd, ³J=14 Hz and 7 Hz, CH₂ βTrp), 5.05 (1H, m, CH αTrp), 5.25 (2H, d,J=7 Hz, CH ₂-p-nitrobenzyl), 6.72 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.89 (2H,d, J_(o)=9 Hz, H₂ and H₆ p-nitrobenzyl), 6.92 (1H, t, J_(o)=7 Hz, H₆Trp), 7.00 (1H, d, J_(m)=2 Hz, H₂ Trp), 7.08-7.15 (4H, m, H₄ and H₇ Trp,H₂ and H₆ phenyl), 7.17 (2H, J_(o)=7 hz, H₃ and H₅ phenyl), 7.24 (1H, t,J_(o)=8 Hz, H₄ phenyl), 7.92 (2H, d, J_(o)=9 Hz, H₃ and H₅p-nitrobenzyl), 8.06 (3H, brs, NH₂ Aib), 8.98 (1H, d, J=8 Hz, NH amide),10.79 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.4 (CH₂—CH₂-phenyl), 29.1 (CH₂βTrp), 32.6 (CH₂—CH₂-phenyl), 45.3 (CH₂-p-nitrobenzyl), 45.7 (CH αTrp),56.8 (Cq Aib), 109.6 (C₃ Trp), 111.8 (C₇ Trp), 118.1 (C₄ Trp), 118.5 (C₅Trp), 121.2 (C₆ Trp), 124.1 (C₂ and C₅ p-nitrobenzyl), 124.8 (C₂ Trp),126.5 (C₂ and C₅ phenyl), 127.2 (C₉ Trp, C₁ and C₆ p-nitrobenzyl), 128.7(C₃, C₄ and C₅ phenyl), 136.4 (C₈ Trp), 140.8 (C₁ phenyl), 143.5 (C₁p-nitrobenzyl), 154.5 (Cq triazole), 154.8 (Cq triazole), 172.0 (COAib).

(S)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 129)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.27 (3H, s, CH₃ Aib), 1.30 (3H, s, CH₃ Aib), 2.81 (4H, m, CH₂—CH ₂-phenyl), 3.34 (2H, d, J=7 Hz, CH₂ βTrp), 3.68 (3H, s, OCH₃), 4.99(2H, s, CH ₂-p-methoxybenzyl), 5.20 (1H, m, CH αTrp), 6.75 (4H, m, CHarp-methoxybenzyl), 6.83 (1H, t, J_(o)=7 Hz, H₅ Trp), 7.03 (1H, t, J_(o)=8Hz, H₆ Trp), 7.04 (1H, d, J=2 Hz, H₂ Trp), 7.10 (2H, d, J_(o)=7 Hz, H₂and H₆ phenyl), 7.13 (1H, d, J_(o)=8 Hz, H₄ Trp), 7.19 (3H, t, J_(o)=7Hz, H₃, H₄ and H₅ phenyl), 7.29 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.01 (3H,brs, NH₂ Aib), 8.94 (1H, d, J=8 Hz, NH amide), 10.78 (1H, d, J=2 Hz, NHindole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 26.6 (CH₂—CH₂-phenyl), 29.2 (CH₂βTrp), 32.7 (CH₂—CH₂-phenyl), 45.3 (CH₂-p-methoxybenzyl), 45.7 (CHαTrp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.9 (C₃ Trp), 111.8 (C₇ Trp), 114.6(C₃ and C₅ p-methoxybenzyl), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆Trp), 124.8 (C₂ Trp), 126.5 (C₄ phenyl), 127.3 (C₉ Trp and C₁p-methoxybenzyl), 127.9 (C₂ and C₆ p-methoxybenzyl), 128.7 (C₂, C₃, C₅and C₆ p-methoxybenzyl), 136.5 (C₈ Trp), 140.9 (C₁ phenyl), 154.4 (Cqtriazole), 154.7 (Cq triazole), 159.2 (C₄ p-methoxybenzyl), 171.9 (COamide).

(R)—N-(1-(4-(4-methoxyphenethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 130)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.30 (3H, s, CH₃ Aib), 1.35 (3H, s, CH₃ Aib), 2.55 (4H, m, CH₂—CH₂-phenyl and CH₂—CH ₂-p-methoxybenzyl), 2.83 (2H, t, J=8 Hz, CH₂—CH₂-phenyl), 3.37 (2H, m, CH ₂—CH₂-p-methoxybenzyl), 3.65 (3H, s, OCH₃),3.77 (1H, m, CH₂ βTrp), 3.89 (1H, m, CH₂ βTrp), 5.20 (1H, m, CH αTrp),6.72 (4H, s, CHar p-methoxybenzyl), 6.94 (1H, t, J_(o)=7 Hz, H₅ Trp),7.02 (1H, t, J_(o)=8 Hz, H₆ Trp), 7.05 (1H, d, J=2 Hz, H₂ Trp), 7.11(2H, d, J_(o)=7 Hz, H₂ and H₆ phenyl), 7.16 (1H, d, J_(o)=7 Hz, H₄ Trp),7.25 (3H m, H₃, H₄, H₅ phenyl), 7.50 (1H, d, J_(o)=8 Hz, H₇ Trp), 8.05(3H, brs, NH₂ Aib), 9.02 (1H, d, J=8 hz, NH amide), 10.83 (1H, d, J=2Hz, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.0 (CH₂—CH₂-phenyl), 29.5 (CH₂βTrp), 32.5 (CH₂—CH₂-phenyl), 35.0 (CH₂—CH₂-p-methoxybenzyl), 44.4(CH₂—CH₂-p-methoxybenzyl), 45.8 (CH αTrp), 55.4 (OCH₃), 56.8 (Cq Aib),109.9 (C₃ Trp), 111.9 (C₇ Trp), 114.2 (C₃ and C₅ p-methoxybenzyl), 118.4(C₄ Trp), 118.9 (C₅ Trp), 121.4 (C₆ Trp), 124.7 (C₂ Trp), 126.5 (C₄phenyl), 127.4 (C₉ Trp), 128.7 (C₂, C₃, C₅ and C₆ phenyl), 129.4 (C₁p-methoxybenzyl), 130.3 (C₂ and C₆ p-methoxybenzyl), 136.5 (C₈ Trp),141.0 (C₁ phenyl), 154.0 (Cq triazole), 154.5 (Cq triazole), 158.6 (C₄p-methoxybenzyl), 171.8 (CO amide).

(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 132)

¹H NMR (300 MHz, DMSO-d⁶, 300° K):

δ(ppm) 1.26 (3H, s, CH₃ Aib), 1.29 (3H, s, CH₃ Aib), 2.95 (4H, m, CH₂—CH ₂-phenyl), 3.40 (2H, m, CH₂ βTrp), 5.26 (1H, m, CH αTrp), 5.37 (2H,s, CH₂-o-pyridyl), 6.83 (1H, t, J_(o)=7 Hz, H₅ Trp), 6.98 (1H, t,J_(o)=8 Hz, H₆ Trp), 7.11-7.30 (10H, m, H₂, H₄ and H₇ Trp, CHar phenyl,H₃ and H₅ o-pyridyl), 7.71 (1H, t, J_(o)=7 Hz, H₄ o-pyridyl), 8.22 (3H,brs, NH₂ Aib), 8.42 (1H, d, J_(αβ)=4 Hz, H₆ o-pyridyl), 9.05 (1H, d, J=8Hz, NH amide), 10.87 (1H, s, NH indole Trp).

¹³C NMR (75 MHz, DMSO-d⁶, 300° K):

δ(ppm) 23.4 (CH₃ Aib), 23.7 (CH₃ Aib), 26.4 (CH₂—CH₂-phenyl), 28.6 (CH₂βTrp), 32.5 (CH₂—CH₂-phenyl), 45.7 (CH αTrp), 47.6 (CH₂ o-pyridyl), 56.8(Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.6 (C₅Trp), 121.2 (C₆ Trp), 122.0 (C₃ o-pyridyl), 123.6 (C₅ o-pyridyl), 126.3(C₂ Trp), 126.6 (C₄ phenyl), 127.3 (C₉ Trp), 128.7 (C₂, C₃, C₅ and C₆phenyl), 136.4 (C₈ trypophane), 137.7 (C₄ o-pyridyl), 140.7 (C₁ phenyl),150.1 (C₆ o-pyridyl), 154.9 (Cq triazole), 155.2 (Cq triazole), 158.7(C₂ o-pyridyl), 172.0 (CO amide).

N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 179)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.26 (s, 3H, CH₃ Aib), 1.30 (s, 3H, CH₃ Aib), 2.82 (m, 4H, CH₂—CH ₉-phenyl), 3.29 (t, 2H, J=8 Hz, CH₂ βTrp), 3.61 (s, 3H, OCH₃), 3.68(s, 3H, OCH₃), 4.85 (d, 1H, J=17 Hz, CH₂-o,p-dimethoxybenzyl), 5.02 (d,1H, J=17 Hz, CH₂-o,p-dimethoxybenzyl), 5.18 (m, 1H, CH αTrp), 6.29 (dd,1H, J_(o)=8 Hz and J_(m)=2 Hz, H₅ o,p-dimethoxybenzyl), 6.40 (d, 1H,J_(o)=8 Hz, H₆ o,p-dimethoxybenzyl), 6.55 (d, 1H, J_(m)=2 Hz, H₃o,p-dimethoxybenzyl), 6.82 (t, 1H, J_(o)=8 Hz, H₅ Trp), 6.99 (t, 1H,J_(o)=8 Hz, H₆ Trp), 7.05 (s, 1H, H₂ Trp), 7.09-7.24 (m, 6H, H₄ Trp andCHar phenyl), 7.27 (d, 1H, J_(o)=8 Hz, H₇ Trp), 7.99 (s, 3H, large, NH₂Aib TFA salt), 8.89 (d, 1H, J=8 Hz, NH amide), 10.77 (s, 1H, NH indoleTrp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 23.6 (CH₃ Aib), 23.7 (CH₃ Aib), 26.5 (CH₂—CH₂-phenyl), 29.2 (CH₂βTrp), 32.7 (CH₂—CH₂-phenyl), 41.6 (CH₂-o,p-dimethoxybenzyl), 45.7 (CHαTrp), 55.7 (OCH₃), 55.9 (OCH₃), 56.7 (Cq Aib), 99.1 (C₃o,p-dimethoxybenzyl), 105.2 (C₅ o,p-dimethoxybenzyl), 110.0 (C₃ Trp),111.8 (C₇ Trp), 115.7 (C₁ o,p-dimethoxybenzyl), 118.3 (C₄ Trp), 118.7(C₅ Trp), 121.3 (C₆ Trp), 126.5 (C₂ Trp and C₆ o,p-dimethoxybenzyl),127.3 (C₉ Trp), 128.1 (C₄ phenyl), 128.7 (C₂, C₃, C₅ and C₆ phenyl),136.4 (C₆ Trp), 140.9 (C₁ phenyl), 154.5 (Cq triazole), 155.0 (Cqtriazole), 157.8 (C₂ o,p-dimethoxybenzyl), 160.9 (C₄o,p-dimethoxybenzyl), 171.7 (CO amide).

N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-tetrahydro-2H-pyran-4-carboxamide(Compound 184)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.20 (m, 1H, H₅ tetrahydropyrane), 1.30 (m, 3H, H₃ and H₅tetrahydropyrane), 2.17 (m, 1H, H₄ tetrahydropyrane), 2.82 (m, 4H, CH₂—CH ₂-phenyl), 3.16 (m, 2H, H₂ and H₆ tetrahydropyrane), 3.31 (dd, 1H,J=14 Hz and 8 Hz, CH₂ βTrp), 3.35 (dd, 1H, J=14 Hz and 7 Hz, CH₂ βTrp),3.66 (s, 3H, OCH₃), 3.72 (m, 2H, H₂ and H₆ tetrahydropyrane), 5.08 (m,2H, CH₂-p-methoxybenzyl), 5.26 (m, 1H, CH αTrp), 6.73 (s, 4H, CHarp-methoxybenzyl), 6.87 (t, 1H, J_(o)=8 Hz, H₅ Trp), 7.02 (m, 2H, H₂ andH₆ Trp), 7.07 (d, 2H, J_(o)=7 Hz, H₂ and H₆ phenyl), 7.18 (m, 3H, H₃, H₄and H₅ phenyl), 7.30 (m, 2H, H₄ and H₇ Trp), 8.52 (d, 1H, J=8 Hz, NHamide), 10.77 (s, 1H, NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 26.3 (CH₂—CH₂-phenyl), 28.8 (C₃ and C₅ tetrahydropyrane), 29.2(CH₂ βTrp), 32.2 (CH₂—CH₂-phenyl), 40.7 (C₄ tetrahydropyrane), 44.8 (CHαTrp), 45.9 (CH₂-p-methoxybenzyl), 55.5 (OCH₃), 66.6 (C₂ and C₆tetrahydropyrane), 109.8 (C₃ Trp), 111.7 (C₇ Trp), 114.5 (C₃ and C₅p-methoxybenzyl), 118.4 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.5(C₂ Trp), 126.7 (C₄ phenyl), 127.2 (C₉ Trp), 127.5 (C₁ p-methoxybenzyl),128.8 (C₂ and C₆ phenyl), 128.7 (C₃ and C₅ phenyl), 127.9 (C₂ and C₆p-methoxybenzyl), 136.4 (C₈ Trp), 140.4 (C₁ phenyl), 154.7 (Cqtriazole), 155.7 (Cq triazole), 159.2 (C₄ p-methoxybenzyl), 174.2 (COamide).

N—((R)-1-(5-((1H-indol-3-yl)methyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide(Compound 185)

¹H NMR (300 MHz, DMSO d⁶, 300° K):

δ(ppm) 1.19 (s, 3H, CH₃ Aib), 1.23 (s, 3H, CH₃ Aib), 3.14 (dd, 1H, J=14Hz and 5 Hz, CH₂ βTrp), 3.34 (dd, 1H, J=14 Hz and 9 Hz, CH₂ βTrp), 3.46(s, 3H, OCH₃), 3.72 (m, 2H, CH ₂-indole), 5.06 (m, 1H, CH αTrp), 5.14(m, 2H, CH₂-m-methoxybenzyl), 6.31 (s, 1H, H₂ m-methoxybenzyl), 6.32 (d,1H, J_(o)=7 Hz, H₆ m-methoxybenzyl), 6.77 (m, 3H, H₅ indole, H₅ Trp andH₄ m-methoxybenzyl), 6.92 (m, 2H, H₆ indole and H₆ Trp), 7.02 (m, 2H, H₂indole and H₂ Trp), 7.26-7.30 (m, 3H, H₅ m-methoxybenzyl, H₄ and H₇indole, H₄ Trp), 7.41 (d, 1H, J_(o)=8 Hz, H₇ Trp), 7.94 (brs, 3H, NH₂Aib TFA salt), 8.87 (d, 1H, J=8 Hz, NH amide), 10.73 (d, 1H, J=2 Hz, NHindole), 10.85 (s, 1H, NH indole Trp).

¹³C NMR (75 MHz, DMSO d⁶, 300° K):

δ(ppm) 21.7 (CH₂-indole), 23.5 (CH₃ Aib), 23.7 (CH₃ Aib), 28.9 (CH₂βTrp), 45.5 (CH αTrp), 46.2 (CH₂-m-methoxybenzyl), 55.2 (OCH₃), 56.7 (CqAib), 108.2 (C₃ indole), 109.8 (C₃ Trp), 111.7 (C₇ Trp), 111.9 (C₇indole and C₂ m-methoxybenzyl), 113.7 (C₄ m-methoxybenzyl), 118.2 (C₆m-methoxybenzyl), 118.4 (C₄ Trp), 118.6 (C₄ indole), 118.9 (C₅ indoleand C₅ Trp), 121.2 (C₆ indole), 121.6 (C₆ Trp), 127.1 (C₉ indole), 127.2(C₉ Trp), 136.4 (C₈ Trp), 136.7 (C₈ indole), 137.5 (C₁ m-methoxybenzyl),154.2 (Cq triazole), 155.3 (Cq triazole), 160.0 (C₃ m-methoxybenzyl),171.8 (CO amide). TABLE 1 Further exemplary embodiments with syntheticsequence and MS data (compounds no. 2, 3, 14, 16, 17, 19-22, 24, 26-35,36-122, 124-126, 128-150, 152-190): Chemical name ESI-MS ESI-MS No.(Chem Draw Ultra 8) (calculated) [found (M + H)+] 2(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4- 559.3 560.4phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 3(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4- 573.3 574.3phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 14(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4- 637.2 638.1bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H- indol-3-yl)ethyl)-2-amino-2-methylpropanamide 16 (R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-hexyl-553.3 554.4 4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 17(R)—N-(1-(4,5-bis(2-(1H-indol-3-yl)ethyl)-4H- 598.3 599.21,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide19 (R)—N-(1-(4-(3-methoxybenzyl)-5-phenethyl- 536.3 537.14H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 20(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 536.3 537.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 21(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,5- 605.3 606.4dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 22(R)—N-(1-(4-(4-methoxybenzyl)-5-(3- 550.3 551.3phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H- indol-3-yl)ethyl)-2-amino-2-methylpropanamide 24 (R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-(3-(1H-612.3 612.8 indol-3-yl)propyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 26(R)—N-(1-(4-(2-methoxybenzyl)-5-phenethyl- 536.3 537.14H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 27(R)—N-(2-(1H-indol-3-yl)-1-(4-(naphthalen-1- 556.3 557.2ylmethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide 28(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,4- 613.2 614.2dichlorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 29(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 563.3 564.1fluorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H- indol-3-yl)ethyl)-2-amino-2-methylpropanamide 30 (R)—N-(1-(4-(4-fluorobenzyl)-5-benzyl-4H- 510.3511.0 1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 31(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 631.3 632.0dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4- carboxamide 32(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 631.3 631.8dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3- carboxamide 33(R)—N-(1-(4-(4-methylbenzyl)-5-(3- 534.3 535.4phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H- indol-3-yl)ethyl)-2-amino-2-methylpropanamide 34 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 559.7559.9 methylbenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 36(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 631.3 631.8dimethoxybenzyl)- 4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2- carboxamide 37(R)—N-(1-(4-(4-methylbenzyl)-5-phenethyl- 520.3 521.04H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 38(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 639.3 639.8dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide 39(R)—N-(1-(5-benzyl-4-(pyridin-2-ylmethyl)- 493.3 493.94H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 40 (2S,4R)—N—((R)-1-(4-(4-methoxybenzyl)-5-564.3 565.0 phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-hydroxypyrrolidine-2- carboxamide 41(S)—N—((R)-1-(4-(4-methoxybenzyl)-5- 562.3 563.0phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide 42(R)—N—((R)-1-(4-(4-methoxybenzyl)-5- 562.3 562.9phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide 43(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 534.3 535.01,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide44 (R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 562.3 563.04H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-4-carboxamide45 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 601.3 602.0methoxybenzyl)- 4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide 46(S)—N—((R)-1-(4-(4-methoxybenzyl)-5- 548.3 548.9phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 47(R)—N—((R)-1-(4-(4-methoxybenzyl)-5- 548.3 548.9phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 48(S)—N—((R)-1-(4-(4-methoxybenzyl)-5- 562.3 563.0phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide 49(R)—N—((R)-1-(4-(4-methoxybenzyl)-5- 562.3 562.9phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide 50(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 508.3 508.94H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)- 2-aminoacetamide 51(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 570.3 571.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 52 N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-570.3 570.9 4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide 53 (R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-561.3 562.4 4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)cyclohexanecarboxamide 54(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl- 571.3 572.54H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-4-carboxamide55 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl- 571.3 572.44H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-3-carboxamide56 (R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 522.3 523.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)- 3-aminopropanamide 57(S)—N—((R)-1-(4-(4-methoxybenzyl)-5- 522.3 523.3phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide 58(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 570.3 571.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-yl)acetamide 59 (R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-584.3 585.3 4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-(pyridin-3-yl)propanamide 60(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl- 579.3 580.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 61(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 639.3 640.5dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2- yl)acetamide 62(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5- 592.3 593.3phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide 63(R)—N-((R)-1-(4-(2,4-dimethoxybenzyl)-5- 592.3 593.3phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide 64(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5- 586.3 587.2phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol- 3-yl)ethyl)picolinamide 65(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5- 586.3 587.2phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol- 3-yl)ethyl)isonicotinamide66 (R)—N-(1-(4-(2,4-dimethoxybenzyl)-5- 587.3 588.2phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide 67 (R)—N-1-(4-(2,4-dimethoxybenzyl)-5-593.3 594.2 phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide 68(S)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5- 578.3 579.4phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 69(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 577.3 578.0dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 70(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4- 617.3 618.0(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2- carboxamide 71(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 626.3 627.2dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide 72(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 632.3 633.2dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2- carboxamide 73(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 625.3 626.3dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 74(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 520.3 520.8dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2- (1H-indol-3-yl)ethanamine 75(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5- 538.3 539.3phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 76(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 557.3 558.04H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)pyrazine-2-carboxamide 77(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 556.3 556.94H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)isonicotinamide 78(R)—N-1-(4-(4-methoxybenzyl)-5-phenethyl- 563.3 564.04H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperazine-2-carboxamide79 (R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 556.3 557.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)picolinamide 80(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 595.3 596.2methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 81(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 602.3 603.3methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide 82(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 568.3 569.31,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- (pyridin-2-yl)acetamide83 (R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 560.3 561.31,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-4-carboxamide 84(R)—N-1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 561.3 562.21,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperazine-2-carboxamide 85(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 555.3 556.21,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)pyrazine-2-carboxamide 86(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 645.3 646.2dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2- (1H-indol-3-yl)ethyl)-2-cis-aminocyclohexanecarboxamide 87(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 601.3 601.9methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide 88(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 601.3 602.2methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide 89(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 587.3 588.2methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 90(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 587.3 588.0methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 91(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 609.3 610.0methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 92(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 623.2 624.1bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H- indol-3-yl)ethyl)-2-amino-2-methylpropanamide 93 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 536.3536.9 methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide 94(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4- 538.3 538.8(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide 95(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-4H-1,2,4- 455.2 456.2triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino- 2-methylpropanamide 96(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-methyl- 455.2 456.44H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 97(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-methyl- 469.3 470.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 98(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4H-1,2,4- 441.3 442.1triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino- 2-methylpropanamide 99(R)—N-(1-(5-((1H-ndol-3-yl)methyl)-4-(2,4- 591.3 592.1dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 100(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-methyl- 476.3 477.44H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 101(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(4- 561.3 562.3methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 102(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl- 552.3 553.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 103(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(2,4- 619.3 620.2dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 104(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4- 545.3 546.4phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 105(R)—N-(1-(5-benzyl-4-phenethyl-4H-1,2,4- 506.3 507.4triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino- 2-methylpropanamide 106(R)—N-(1-(5-benzyl-4-(2,2-diphenylethyl)-4H- 582.3 583.31,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide107 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,2- 635.3 636.4diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 108(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-benzyl- 552.3 553.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 109(R)—N-(1-(4,5-dibenzyl-4H-1,2,4-triazol-3-yl)- 492.3 493.32-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 110(R)—N-(1-(5-benzyl-4-hexyl-4H-1,2,4-triazol- 486.3 487.43-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 111(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-benzyl- 545.3 546.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 112(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl- 552.3 553.14H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 113 (R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-566.3 567.3 phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 114(R)—N-(1-(4-(4-bromobenzyl)-5-benzyl-4H- 570.2 571.01,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide115 (R)—N-(1-(4-(2-methoxybenzyl)-5-benzyl-4H- 522.3 523.01,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide116 (S)—N-(1-(4-(2,4-dimethoxybenzyl)-5- 566.3 567.0phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 117(R)—N-(1-(4,5-diphenethyl-4H-1,2,4-triazol-3- 520.3 521.1yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 118(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-benzyl- 560.2 561.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 119(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 451.3 452.1dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2- (1H-indol-3-yl)ethanamine 120(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H- 483.3 484.01,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2- methylpropanamide 121(R)—N-(1-(4-(4-fluorobenzyl)-5-phenethyl-4H- 524.3 524.91,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide122 (R)—N-(1-(4-(3,4-dichlorobenzyl)-5-phenethyl- 574.2 574.94H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 124(R)—N-(1-(4-(4-methylbenzyl)-5-benzyl-4H- 506.3 507.31,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide125 (S)—N-(1-(4-(4-methoxybenzyl)-5-(3- 550.3 551.3phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H- indol-3-yl)ethyl)-2-amino-2-methylpropanamide 126 (S)—N-(1-(4-(4-methoxybenzyl)-5-benzyl- 522.3523.4 1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 128(R)—N-(1-(4-(4-nitrobenzyl)-5-phenethyl-4H- 551.3 551.91,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- amino-2-methylpropanamide129 (S)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl- 536.3 537.04H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 130 (R)—N-(1-(4-(4-methoxyphenethyl)-5-550.3 551.0 phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 131(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4- 512.2 512.8(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide 132(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4- 507.3 508.4(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide 133(R)—N-(-2-(1H-indol-3-yl)-1-(5-phenethyl-4- 533.3 534.0(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-3-carboxamide 134(S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl- 546.3 547.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)pyrrolidine-2-carboxamide135 N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 506.3 507.31,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- aminoacetamide 136N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 609.3 610.4methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide 137(2R)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl- 560.3 561.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-2-carboxamide138 N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 554.3 555.31,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)picolinamide 139N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 569.3 570.31,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopyridine-3-carboxamide 140(2S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl- 520.3 521.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)- 2-aminopropanamide 141N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 554.3 555.41,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)isonicotinamide 142N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4- 518.3 519.3phenyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine- 4-carboxamide 143(2S)—N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl- 504.3 505.14-phenyl-4H-1,2,4-triazol-3- yl)ethyl)pyrrolidine-2-carboxamide 144N((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4- 464.3 465.1phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2- aminoacetamide 145N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4- 526.3 527.2phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin- 2-yl)acetamide 146N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4- 512.3 513.4phenyl-4H-1,2,4-triazol-3- yl)ethyl)picolinamide 147N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 579.3 580.1ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H- indol-3-yl)ethyl)picolinamide148 N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 593.3 594.2ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 149N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 531.3 532.2ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 150(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 571.3 572.4ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 152N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 547.3 548.0methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 153N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl- 576.3 577.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-trans-aminocyclohexanecarboxamide 154N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 568.3 569.31,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- (pyridin-3-yl)acetamide155 (3S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl- 560.3 561.54H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-3-carboxamide156 N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H- 568.3 569.11,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- aminobenzamide 157N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl- 551.3 552.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)picolinamide 158N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl- 557.3 558.14H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-4-carboxamide159 N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4- 572.3 573.4dimethoxyphenyl)-5-phenethyl-4H-1,2,4- triazol-3-yl)ethyl)picolinamide160 N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4- 586.3 587.3dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 161N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4- 573.3 574.2dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)pyrazine-2-carboxamide 162N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4- 524.3 525.3dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-aminoacetamide 163N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4- 578.3 579.4dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide 164N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)- 513.3 514.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)picolinamide 165N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)- 465.3 466.44H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)- 2-amino-acetamide 166N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)- 519.3 520.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-4-carboxamide167 N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)- 493.3 494.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 168N—((R)-1-(5-(4-methoxybenzyl)-4-phenethyl- 536.3 537.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 169N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)- 513.3 514.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)picolinamide 170N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)- 465.3 466.14H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)2-amino-acetamide 171(R)-benzyl-3-(2-aminoisobutyramido)-3-(5- 594.3 595.2(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-propanoate 172N—((R)-1-(5-benzyl-4-((pyridin-3-yl)methyl)- 493.3 494.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 173 N—((R)-1-(4-benzyl-5-phenethyl-4H-1,2,4-506.3 507.3 triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 174 N—((R)-2-(1H-indol-3-yl)-1-(4-methyl-5- 450.3451.3 phenethyl-4H-1,2,4-triazol-3- yl)ethyl)picolinamide 175N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl- 531.3 532.44H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 176N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl- 555.3 556.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)benzamide 177(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl- 635.3 637.04H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N- phenylmethanesulfonylamine178 (R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl- 635.3 636.34H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N- tosylethanamine 179N—((R)-1-(4-(2,4-dimethoxybenzyl)-5- 566.3 567.2phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 180N-1-((R)-1-(4-(2,4-dimethoxybenzyl)-5- 524.3 525.2phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)ethane-1,2-diamine 181N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl- 496.3 497.14H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 182N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl- 516.3 517.14H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)picolinamide 183N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl- 522.3 523.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)piperidine-4-carboxamide184 N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl- 563.3 564.24H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-tetrahydro-2H-pyran-4-carboxamide 185N—((R)-1-(5-((1H-indol-3-yl)methyl)-4-(3- 561.3 562.2methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 186(2S)—N—((R)-1-(4-(4-methoxybenzyl)-5- 598.3 599.1phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-3-phenylpropanamide 187(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4- 674.3 675.0dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine 188N—((R)-1-(4-(2,4-dimethoxybenzyl)-5- 626.3 627.3phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-azidobenzamide 189N-benzyl-(R)-1-(4-(2,4-dimethoxybenzyl)-5- 571.3 572.3phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol- 3-yl)ethanamine 190(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4- 585.3 586.2methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2,5-dihydro-1H-pyrrole-2- carboxamideII) GHS-R 1a Receptor-Ligand Binding Assay (Membrane Preparations fromTransfected LLC PK-1 Cells)

The GHS-R 1a receptor binding/affinity studies were performed accordingto Guerlavais et al. (J. Med. Chem. 2003, 46: 1191-1203).

Isolated plasma membranes from LLC PK-1 cells, a renal epithelial cellline originally derived from porcine kidneys (ECACC No. 86121112) (10 μgof protein), that were transiently transfected with human GHS-R 1a cDNA(Guerlavais et al., J. Med. Chem. 2003, 46: 1191-1203), were incubatedin homogenization buffer HB [50 mM Tris (pH 7,3), 5 mM MgCl₂, 2,5 mMEDTA, and 30 μg/mL bacitracin (Sigma)] for 60 min at 25° C.(steady-state conditions) with 60 pM ¹²⁵I-His⁹-ghrelin (Amersham) in thepresence or absence of competing compounds (compounds of the invention).

The binding affinity for each compound to be tested for the human GHS-R1a was measured by displacement of the radiolabelled ghrelin withincreasing concentrations of the test compound (10⁻¹¹M to 10⁻²M) (eachexperiment being performed in triplicates).

Nonspecific binding was defined using an excess (10⁻⁶ M) of ghrelin. Thebinding reaction was stopped by addition of 4 mL of ice-cold HB followedby rapid filtration over Whatman GP/C filters presoaked with 0.5%polyethyleneimine to prevent excessive binding of radioligand to thefilters. Filters were rinsed three times with 3 mL of ice-cold washbuffer [50 mM Tris (pH 7.3), 10 mM MgCl₂, 2.5 mM EDTA, and 0.015% (w/v)X-100 Triton], and the radioactivity bound to membranes was measured ina gamma-counter (Kontron Analytical Gamma Matic, Automatic gammacounting system).

The concentration of test compounds required to inhibit radiolabelledghrelin binding by 50% (IC₅₀) was determined by fitting competitivebinding curves using non-linear regression (PRISM 3.0, Graph Pad SanDiego, USA).

In the following table 2 results obtained for selected compounds of theinvention are presented in comparison to an example of the prior art.IC₅₀ values given are the mean of at least two independent experimentsperformed in triplicates.

FIGS. 1-13 show the measured competition plots of the GHS-R 1aReceptor-ligand binding assay with ¹²⁵I-His⁹-ghrelin and the selectedcompounds 9, 31, 39, 45, 50, 62, 64, 71, 73, 74, 79, 81 and 90. TABLE 2GHS-R 1a Receptor-ligand binding assay test results (IC₅₀ values for anumber of selected exemplary compounds) GHS-R 1a No. IC₅₀ [nM] Chemicalname  1 160 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide  2 81(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide  3 14(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 4 220 (R)—N-(1-(5-benzyl-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide  5125 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide  6 18(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide  7 120(R)—N-(1-(4-(3-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide  8 18(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide  9 46(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 10 32(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 11 137(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 12 6(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 13 138(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 14 150(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 15 120(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 16240 (R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 17156 (R)—N-(1-(4,5-bis(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 18 83(S)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 19 78(R)—N-(1-(4-(3-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 20 14(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 21203 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,5-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 22 12(R)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide23 37 (R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 24 29(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-(3-(1H-indol-3-yl)propyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 25 96(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2-methoxy)benzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 26 56(R)—N-(1-(4-(2-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 27126 (R)—N-(2-(1H-indol-3-yl)-1-(4-(naphthalen-1-ylmethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2- methylpropanamide 2879 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,4-dichlorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 29 66(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-fluorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide30 171 (R)—N-(1-(4-(4-fluorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 31 0.5(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide 32 10.3(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide 33 30(R)—N-(1-(4-(4-methylbenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide34 28 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 36 53 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide 37 136(R)—N-(1-(4-(4-methylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 38112 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide 40 249(2S,4R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-hydroxypyrrolidine-2-carboxamide 41 16(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3- carboxamide 42 7(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3- carboxamide 43 44(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 44 0.6(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4- carboxamide 45 0.3(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4- carboxamide46 12 (S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2- carboxamide 47 27(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2- carboxamide 48 11(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2- carboxamide 49 23(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2- carboxamide 50 56(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 51 3(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2- yl)acetamide 53 18(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)cyclohexanecarboxamide 54 35(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4- carboxamide 55 11(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3- carboxamide 56 59(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-aminopropanamide 57 140(S)—N-((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide 58 29(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3- yl)acetamide 59 173(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-(pyridin-3- yl)propanamide 60 61(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2- yl)acetamide 61 34(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 62 0.9(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4- carboxamide 63 210(R)—N-((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2- carboxamide 641.1 (R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 65 58(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide 66 8(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2- carboxamide 67 35(R)—N-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-piperazine-2- carboxamide 68 44(S)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2- carboxamide 6938 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 70 6(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 71 19(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide 72 32(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-piperazine-2-carboxamide 73 1.8(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 75 140(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 76 14(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2- carboxamide 77 119(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide 78 54(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-piperazine-2- carboxamide 79 0.7(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 80 1.9(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 81 18(R)—N-(1-(5-((1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-piperazine-2- carboxamide82 51 (R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 83 19(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide 84 247(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-piperazine-2-carboxamide 85 89(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide 86 143(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-cis-aminocyclohexanecarboxamide 87 10(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide 88 29(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide 89 9(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 90 28(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide 91 11(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide 92 200(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 94 255(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4- carboxamide 108  250(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 136 106 (R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide 138  44N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 146  105N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide 147  49N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 148  96N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2- yl)acetamide152  138 N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2- aminoacetamide 155 188 (3S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3- carboxamide 157  160N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 158  70N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4- carboxamide 159  33N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide 160  121N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2- yl)acetamide 163 63 N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4- carboxamide 164  207N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 173  114N—((R)-1-(4-benzyl-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide 175  140N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 176 80 N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)benzamide 179  62N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- methylpropanamide 180 189 N-1-((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)ethane-1,2- diamine 182  81N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide 184  5.9N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-tetrahydro-2H-pyran-4- carboxamide186  175 (2S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-3- phenylpropanamide187  66 (R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine 188  87N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-azidobenzamide 190  12(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2,5-dihydro-1H-pyrrole-2-carboxamide Example 39 ca. 5000(R)—N-(1-(5-(tert-butylthio)-4-(furan-2-ylmethyl)-4H-1,2,4- fromtriazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2- WO 00/54729methylpropanamide A2 Example 8 from ca. 20000(S)—N-(1-(4-benzyl-5-(tert-butylthio)-1,2,4-triazol-3-yl)-2- WO 00/54729(benzyloxy)ethyl)-2-amino-2-methylpropanamide A2 Example 3 from ca. 3000(R)—N-(1-(1-methylpropanoate-tetrazol-5-yl)-2-(1H-indol- WO 00/547293-yl)ethyl)-2-amino-2-methylpropanamide A2 Example from ca. 25000(S)—N-(1-(1-benzyl-tetrazol-5-yl)-2-(benzyloxy)ethyl)-2- page 175,amino-2-methylpropanamide WO 00/54729 A2III) In Vitro Intracellular Calcium Release Assay using Human GHS-R 1aTransfected CHO Cells

The potential of the compounds of the invention to modulate GHS receptoractivity was assessed by an in vitro intracellular Calcium release assayemploying CHO cells that were transfected with human GHS-R 1a.

Release of intracellular calcium or inhibition thereof was measuredusing the fluorescent calcium indicator assay (FLIPR) and Fluo-4 AM.

CHO cells (CHO-KI Chinese Hamster Ovary cell line, ATCC No. CCL-61) weretransiently transfected with human GHS-R 1a cDNA by electroporation andplated into 96-well black bottom plates (Corning 3603) (80,000cells/well). Transient transfections were performed using the EasyjectOptima Electroporator (Equibio), according to the manufacturer'sinstructions.

Transfected cells were grown in Dulbecco's modified Eagle's mediumwithout phenol red, supplemented with 10% (v/v) non-essential aminoacids, 2 nM glutamine and streptomycin-penicillin (250 μg/ml-250 u/ml)(all purchased from Cambrex) at 37° C., 5% CO₂ in a humidifiedatmosphere for 24 hours.

After incubation, transfected cells were washed with 150 μl Buffer A[Hanks' balanced salt solution (Sigma H-6648), 0.5% (v/v) BSA (SigmaA-7906), 20 mM CaCl₂, 2.5 mM probenecid (pH 7.4, dissolved in 1M NaOH)(Sigma P-8761)] and were then loaded with fluorescent calcium indicatorFluo-4 AM (10⁻⁶ M) (Interchim UP72972) prepared in Buffer A,additionally containing 0.06% pluronic acid (Molecular probes P-6867) (amild-ionic detergent which facilitates Fluo-4AM ester loading).(Loading:100 μl per well of Buffer A containing 120 μl/ml Pluronic Acid and 1 μMFluo-4AM was added to the cells).

After loading with Fluo-4 AM, transfected cells were incubated for 1hour in the dark at 37° C.

Compounds to be tested were dissolved in Buffer A in triplicates at aconcentration of 10⁻⁶ M and distributed into another 96-well plate(Fisher Labosi A1210500).

Following incubation, excess Fluo-4AM was removed, 100 μl of Buffer Awas added to each well at room temperature and immediately removed byaspiration. This was then repeated, before adding 50 μl Buffer A to eachwell.

Transfected cells were further incubated room temperature for 30 min toallow complete de-esterification of intracellular Fluo-4AM esters.

Subsequently, both plates, the black-bottom plate containing transfectedcells and the microtiter plate containing the compounds to be tested,were then placed into a temperature-regulated (25° C.) FlexStationmachine (benchtop scanning fluorometer Flex Station II, MolecularDevices, Sunnyvale, Calif., USA) for fluorescence output measurements.

Since Fluo-4AM exhibits a large fluorescence intensity increase uponbinding of calcium, fluorescence output can be used directly as aproportional measure of intracellular calcium release.

Basal fluorescence output from the transfected cells was measured for 15sec and then 50 μl of the compounds to be tested were automaticallydistributed into the wells containing the transfected cells. Thefluorescence output was then recorded for a further 45 sec.

Excitation and emission wavelengths were 485 nm and 525 nm,respectively. Basal fluorescence intensity of Fluo-4AM-loadedtransfected cells without compounds to be tested varied between 800-1200arbitrary units, whereas maximal fluorescence output of dye-loadedtransfected cells upon incubation with the compounds to be tested variedbetween 5000-7000 arbitrary units and was equivalent to that achieved bystimulation of dye-loaded transfected cells with 10⁻⁶ M ghrelin.

For each compound to be tested change in fluorescence output uponaddition of the respective compound was compared with the basalfluorescence output measured with a negative control, i.e. addition 50μl of buffer A to transfected cells only.

The ability and extent to which each compound to be tested causedcalcium release was determined relative to the basal level (0%) and themaximum level (100%) achieved with 1 μM ghrelin.

For the compounds to be tested that were identified as GHS receptoragonists, EC₅₀ and KI values were determined using a dose-responsecurve.

As for the compounds to be tested that were identified as GHS receptorantagonists, IC₅₀ and Kb (antagonist dissociation constant) values weredetermined using antagonist inhibition curves in the presence of 10⁻⁷ Mghrelin (submaximal concentration). IC₅₀ values were calculated as themolar concentration of GHS receptor antagonist that reduced the maximalresponse of ghrelin by 50%. Kb values were estimated using theCheng-Prusoff Equation (Lazareno S and Birdsall N J, Trends PharmacolSci. 1993, 14(6):237-239).

FIGS. 14-40 show the calculated dose-response plots of the in vitrointracellular Calcium release assay with human GHS-R 1a transfected CHOcells of the selected compounds 1, 9, 12, 20, 22, 31, 39, 41, 42, 45,46, 47, 48, 49, 50, 51, 55, 62, 64, 67, 71, 73, 74, 79, 81, 90 andghrelin as well as individual EC₅₀ and KI values for agonistic compoundsand IC₅₀ and Kb values for antagonistic compounds.

IV) Assaying In Vivo GH Concentration in the Plasma of Male Rat Pups

GH plasma concentrations of male rat pubs were assayed to characterizethe modulation effect (antagonistic or agonistic) of the compounds ofthe invention being GHS receptor analogue ligands.

In principle, assaying in vivo GH concentration in rat plasma wasperformed according to Torsello et al. (Eur. J. Pharmacol. 1998, 360:123-129).

Male Sprague-Dawley rat pups (Charles River, Calco, Italy) wereseparated on postnatal day seven from their mothers and randomlyredistributed to the dams, so that each one nurtured ten to twelve pups.On postnatal day ten, the pups were again separated from their mothers.

The compounds to be tested were dissolved in solvent [DMSO (0.4% oftotal volume), distilled water (4% of total volume), brought to thefinal volume with physiological saline].

One hour after separation from their mothers, the pups were givenisovolumetric amounts of the compounds to be tested (160 μg/kg bodyweight s.c.) at time −10 min and then administered with hexarelin (80μg/kg body weight s.c.) or solvent at time 0 min before being killed 15min later by decapitation. Trunk blood was collected, immediatelycentrifuged and plasma samples were stored at −20° C. until assayed forthe determination of GH concentrations.

Plasma GH concentrations were measured using a rat growth hormone enzymeimmunoassay kit (SPIbio, France, cat. no. 589601) according to themanufacturer's instructions. Values are expressed in terms of NIDDKrat-GH-RP2 standard (potency 2 IU/mg) as ng/mL of plasma

The limit of detection calculated as the concentration producing 15%displacement of initial tracer was 0.5 ng/ml; intra-assay andinter-assay coefficient of variation are 4% (n=24) and 14% (n=9).

In the following table 3 results obtained for selected compounds of theinvention are presented. TABLE 3 Relative GH concentration in rat plasmaafter treatment with selected compounds of the invention (160 μg/kg bodyweight s.c.) and/ or hexarelin (80 μg/kg body weight s.c.) and/orsolvent Treatment GH concentration (ng/mL) solvent 4,008 ± 0,469hexarelin 162,839 ± 21,095  compound 1 n.d. compound 1 + hexarelin 80.22± 18.66 compound 12  4.0 ± 0.12 compound 12 + hexarelin 200.0 ± 19.7 compound 20 5.27 ± 0.59 compound 20 + hexarelin 220.51 ± 15.52  compound22 4.88 ± 0.33 compound 22 + hexarelin 239.91 ± 19.75  compound 47 5,658± 1,192 compound 47 + hexarelin 160,857 ± 13,52  compound 39 5,509 ±1,950 compound 39 + hexarelin 82,481 ± 11,530 compound 31 119,937 ±33,054  compound 31 + hexarelin 103,528 ± 14,094  compound 48 6,096 ±2,091 compound 48 + hexarelin 145,946 ± 12,159  compound 44 87,520 ±15,066 compound 44 + hexarelin 100,52 ± 12,112 solvent 2,237 ± 0,073hexarelin 170,101 ± 13,226  compound 9 13,016 ± 1,960  compound 9 +hexarelin 183.562 ± 16.729  compound 39 5.509 ± 1.95  compound 39 +hexarelin 82.481 ± 11.53  compound 50 9.852 ± 1.040 compound 50 +hexarelin 164.459 ± 4.443  compound 64 13.056 ± 2.169  compound 64 +hexarelin 138.394 ± 14.580  solvent 10,729 ± 2,027  hexarelin 253,820 ±12,268  compound 71 15,326 ± 1,355  compound 71 + hexarelin 173,611 ±18,444  compound 74 10,571 ± 0,791  compound 74 + hexarelin 194,564 ±7,658  compound 81 18,634 ± 2,933  compound 81 + hexarelin 216,575 ±19,734  compound 90 16,857 ± 2,152  compound 90 + hexarelin 218,844 ±19,723 V) Assaying the Feeding Behavior (Food Intake) of Young-Adult Male Rats

The impact of compounds of the invention being GHS receptor analogueligands on the feeding behaviour, i.e. food intake, of young-adult malerats was assayed.

In principle, assaying the feeding behavior (food intake) of young-adultmale rats was performed according to Torsello et al. (Eur. J. Pharmacol.1998, 360: 123-129).

For the assay, young-adult male Sprague-Dawley rats (Charles River,Calco, Italy), weighing 200-250 g, were used.

Rats had 1 week of acclimation in individual home cages, and animal roomconditions (22±2° C., 65% humidity, artificial light from 08.00 to 20.00h). The following week, they were daily trained to mimic theexperimental procedure. Rats maintained free access to dry pellets andtap water throughout the whole experimental period. At the end oftraining, rats were administered (around 10.00-11.00 a.m.)subcutaneously with the compounds to be tested (160 μg/kg body weight)and/or hexarelin (80 μg/kg body weight) and/or solvent [DMSO (0.4% oftotal volume), distilled water (4% of total volume), brought to thefinal volume with physiological saline].

Hexarelin was used to study the effects of the compounds to be tested onstimulated feeding behavior. Immediately after the injections, theanimals were returned to their home cages, which contained a knownamount of standard rat chow and ad libitum water. Every hour for thefollowing 6 hours, the remaining food was carefully collected andweighed to the nearest 0.1 g. Food intake was normalized for the bodyweight of the rats and expressed as grams of food eaten per 100 g bodyweight of rats.

In the following table 4 results obtained for selected compounds of theinvention are presented. TABLE 4 Cumulative food intake (g food/100 gbody weight) of young-adult rats after 2 hours and 6 hours and aftertreatment with selected compounds of the invention (160 μg/kg bodyweight s.c.) and/or hexarelin (80 μg/kg body weight s.c.) and/or solventCumulative Cumulative food intake food intake Treatment (after 2 hours)(after 6 hours) solvent  0.003 ± 0.0015  0.017 ± 0.0026 hexarelin 0.533± 0.194 1.0014 ± 0.1973 compound 1  0.02 ± 0.002 0.06 ± 0.03 compound1 + hexarelin 0.06 ± 0.02 0.33 ± 0.21 compound 12 0.034 ± 0.011  0.06 ±0.019 compound 12 + hexarelin 0.13 ± 0.07 0.48 ± 0.22 compound 20 0.01 0.2 ± 0.19 compound 20 + hexarelin 0.53 ± 0.21 0.63 ± 0.19 compound 220.01 0.44 ± 0.2  compound 22 + hexarelin 0.67 ± 0.12 0.86 ± 0.18compound 47 0.006 ± 0.002 0.02 ± 0   compound 47 + hexarelin  0.35 ±0.201  0.47 ± 0.1943 compound 44  0.43 ± 0.0721 0.7075 ± 0.1471 compound44 + hexarelin 1.2667 ± 0.1319 1.4033 ± 0.1177 solvent 0.184 ± 0.1110.497 ± 0.183 hexarelin 0.536 ± 0.176 0.549 ± 0.169 compound 9 0.01 ±0   0.01 ± 0   compound 9 + hexarelin 0.0104 ± 0.0032 0.0231 ± 0.0032solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 1.060 ± 0.143 1.138 ±0.114 compound 13 0.057 ± 0.057 0.167 ± 0.167 compound 13 + hexarelin0.731 ± 0.318 0.792 ± 0.337 solvent 0.184 ± 0.111 0.497 ± 0.183hexarelin 1.060 ± 0.143 1.138 ± 0.114 compound 17 0.001 ± 0.001 0.2661 ±0.166  compound 17 + hexarelin 0.0501 ± 0.049  0.846 ± 0.411 solvent0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.428 ± 0.192 0.588 ± 0.303compound 24 0.008 ± 0.008 0.215 ± 0.200 compound 24 + hexarelin 0.586 ±0.252 0.912 ± 0.359 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.627± 0.211 0.778 ± 0.218 compound 30 0.264 ± 0.244 0.277 ± 0.246 compound30 + hexarelin 1.350 ± 0.177 1.449 ± 0.213 solvent 0.184 ± 0.018 0.399 ±0.201 hexarelin 0.278 ± 0.078 0.883 ± 0.259 compound 38 0.001 ± 0   0.076 ± 0.096 compound 38 + hexarelin 0.002 ± 0.002 0.478 ± 0.141solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.26 ± 0.13 0.78 ± 0.25compound 49 0.004 ± 0.004 0.004 ± 0.004 compound 49 + hexarelin 0.057 ±0.037 0.558 ± 0.212 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.536± 0.176 0.594 ± 0.169 compound 50 0.012 ± 0.008 0.039 ± 0.011 compound50 + hexarelin 0.003 ± 0.002 0.017 ± 0.001 solvent 0.184 ± 0.111 0.497 ±0.183 hexarelin 0.427 ± 0.16  0.688 ± 0.203 compound 64 0.012 ± 0.0080.039 ± 0.011 compound 64 + hexarelin 0.012 ± 0.004 0.021 ± 0.007solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.696 ± 0.267 0.74 ± 0.27compound 71 0.522 ± 0.283 0.53 ± 0.28 compound 71 + hexarelin 0.117 ±0.074 0.20 ± 0.01 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin  0.70 ±0.116 1.221 ± 0.06  compound 72 0.008 ± 0.003 0.011 ± 0    compound 72 +hexarelin 0.634 ± 0.33  0.746 ± 0.31  solvent 0.184 ± 0.111 0.497 ±0.183 hexarelin 1.031 ± 0.219 1.455 ± 0.192 compound 80 0.145 ± 0.1430.346 ± 0.159 compound 80 + hexarelin 0.475 ± 0.196 0.733 ± 0.238solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.696 ± 0.267 0.74 ± 0.27compound 81 0.017 ± 0.004 0.03 ± 0   compound 81 + hexarelin  0.024 ±0.0101 0.116 ± 0.077 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.412± 0.173 0.68 ± 0.29 compound 81 0.034 ± 0.003 0.346 ± 0.179 compound81 + hexarelin  1.4 ± 0.35 1.665 ± 0.345 solvent 0.184 ± 0.111 0.497 ±0.183 hexarelin 0.323 ± 0.131 0.45 ± 0.17 compound 90 0.014 ± 0.0010.035 ± 0.003 compound 90 + hexarelin 0.054 ± 0.041 0.069 ± 0.041VI) Motilin Receptor-Ligand Binding Assay (Using Human RecombinantHEK-293 Cells)

Motilin Receptor binding/affinity studies were performed as described byFeighner S D et al. (Science 1999, 284: 2184-2188). The assays were rununder the following conditions:

Source: Human recombinant HEK-293 cells [Motilin-Receptor 1a (MTL-R1a)]

Ligand: 0.1 nM [¹²⁵I] Motilin (human, porcine)

Vehicle: 1% DMSO

Incubation Time/Temperature: 2.5 hours at 25° C.

Incubation Buffer: 50 mM Tris, pH 7, 4, 10 mM MgCl₂, 0.5% BSA

Non-Specific Ligand: 1 μM Motilin (human, porcine)

Compounds of the invention were tested in concentrations comprising 0.01μM, 0.1 μM, 1 μM and 10 μM.

IC₅₀ values were determined by a non-linear, least square regressionanalysis using Data Analysis Toolbox (MDL Information Systems, USA).

In the following table 5 results obtained for selected compounds of theinvention are presented. TABLE 5 Motilin Receptor-ligand binding assaytest results (IC₅₀ values for a number of selected exemplary compounds)MTL-R 1a No. IC₅₀ [μM] Chemical name 44 1,61(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4- carboxamide, 641,39 (R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3- yl)ethyl)picolinamide,VII) Study of Anti-Cachectic Effects in an Adjuvant-Induced ArthritisModel System

The effectiveness of compounds of the invention in the treatment ofcachexia was investigated according to Ibanez de Caceres I et al. (JEndocrinol. 2000, 165(3): 537-544) using a cachexia model system(Roubenoff R et al., Arthritis Rheum. 1997, 40(3): 534-539).

Table 6 shows the anti-cachetic effect of compound 44 (0.1 μg/kg/days.c. injection) in arthritic rats in comparison to adjuvant inducedarthritis without medical treatment. TABLE 6 Body weight change in gram(mean of 6 animals per group) Day 3 Day 6 Day 10 Day 13 Day 15 Day 17Rats with −3.02 2.95 11.97 9.32 −2.78 −8.27 adjuvant induced arthritis +vehicle Arthritic rats + −5.32 2.98 14.92 19.08 7.05 1.47 treatment withcompound 44 (0.1 μg/kg/day s.c.)VIII) Study of Anti-Inhibitory Effects of Isoproterol-Induced Lipolysisin Adipocyte Models

The effectiveness of compounds of the invention in the inhibition of theunacylated ghrelin-induced inhibition of isoproterol-induced lipolysiswas investigated using adipocyte models.

Isolation of Primary Mouse Adipocytes

Mice were fed with high fat diet induce obesity (60% of lipids) startingat 4 weeks of age for 12 and 18 weeks.

White adipose tissue from epididymal fat was minced and digested inKrebs-Ringer-Bicarbonate-Hepes (KRBH) buffer (20 mM Hepes pH 7.4, 120 mMNaCl, 4.7 mM KCl, 1.2 mM K₂HPO₄, 2.5 mM CaCl₂, 1.2 mM MgSO₄, 24 mMNaHCO₃) satured with CO₂ containing glucose (1 mg/mL), 1% BSA andcollagenase (2 mg/g tissue). The digestion was made under constantshaking (250 rpm) at 37° C. for 45 minutes.

The cell suspension was filtered through a nylon mesh to separate theadipocytes from tissue fragments, and washed three times in 3 mL of warmKRBH 1% BSA.

The cells was resuspended in KRBH 1% BSA and incubated in shaker (75rpm) at 37° C. for 30 minutes.

Lipolysis Assay

Lipolysis in primary adipocytes cells was induced with 30 nM ofisoproterenol in KRBH 4% BSA for 90 minutes with constant (125 rpm)shaking at 37° C.

Lipolysis in differentiated cells was induced with 30 nM ofisoproterenol in DMEM FBS free for 90 minutes at 37° C. with shakingevery 15 minutes.

The inhibitory effect of unacylated ghrelin (UAG) on isoproterenolinduced lipolysis was documented with increasing concentration of UAGfrom 10⁻¹¹ M to 10⁻⁶ M in presence or in absence of selected compoundsof the invention at 10⁻⁷ M.

The lipolysis index was assessed by measuring glycerol release followingtriglyceride hydrolysis.

The antagonistic effect was determined as follows:${{pA}\quad 2} = {{- \log}\frac{\left\lbrack {{concentration}\quad{of}\quad{competitor}\quad(M)} \right\rbrack}{{Ratio} - 1}}$with${Ratio} = \frac{{EC}\quad 50\quad{in}\quad{presence}\quad{of}\quad{competitor}\quad(M)}{{EC}\quad 50\quad{in}\quad{absence}\quad{of}\quad{competitor}\quad(M)}$

FIGS. 41-46 show the effects of selected compounds 9, 38, 50, 64, 74, 81on the isoprorerenol-induced lipolysis inhibition curve of unacylatedghrelin (UAG) in primary adipocytes from mice under diet-inducedobesity.

The above written description of the invention provides a manner andprocess of making and using it such that any person skilled in this artis enabled to make and use the same, this enablement being provided inparticular for the subject matter of the appended claims, which make upa part of the original description.

As used herein, the phrases “selected from the group consisting of,”“chosen from,” and the like include mixtures of the specified materials.Terms such as “contain(s)” and the like as used herein are open termsmeaning ‘including at least’ unless otherwise specifically noted.

All references, patents, applications, tests, standards, documents,publications, brochures, texts, articles, etc. mentioned herein areincorporated herein by reference. Where a numerical limit or range isstated, the endpoints are included. Also, all values and subrangeswithin a numerical limit or range are specifically included as ifexplicitly written out.

The above description is presented to enable a person skilled in the artto make and use the invention, and is provided in the context of aparticular application and its requirements. Various modifications tothe preferred embodiments will be readily apparent to those skilled inthe art, and the generic principles defined herein may be applied toother embodiments and applications without departing from the spirit andscope of the invention. Thus, this invention is not intended to belimited to the embodiments shown, but is to be accorded the widest scopeconsistent with the principles and features disclosed herein.

The invention method, compounds and compositions are preferably used bysubjects desirous of the benefits noted herein, subjects “in need of”these benefits. Such subjects are typically suffering from physiologicaland/or pathophysiological conditions such as those selected from thegroup consisting of acute fatigue syndrome and muscle loss followingelection surgery, adipogenesis, adiposity, age-related decline of thymicfunction, age-related functional decline (ARFD) in the elderly, agingdisorder in companion animals, Alzheimer's disease, anorexia; anxiety,blood pressure (lowering), body weight gain/reduction, bone fracturerepair (acceleration), bone remodeling stimulation, cachexia and proteinloss reduction due to chronic illness such as cancer or AIDS, cardiacdysfunctions, cardiomyopathy, cartilage growth stimulation, catabolicdisorders in connection with pulmonary dysfunction and ventilatordependency, catabolic side effects of glucocorticoids, catabolic stateof aging, central nervous system disorders (in combination withantidepressants), chronic dialysis, chronic fatigue syndrome (CFS),cognitive function improvement, complicated fractures, complicationsassociated with transplantation, congestive heart failure (alone/incombination with corticotropin releasing factor antagonists), Crohn'sdisease and ulcerative colits, Cushing's syndrome, dementia,depressions, short-, medium- and/or long-term regulation of energybalance, short-, medium- and/or long-term regulation of food intake(stimulation and/or inhibition), fraility, gastrectomy (ghrelinreplacement therapy), gastric postoperative ileus, glycemic controlimprovement, growth hormone release stimulation in the elderly, growthhormone replacement in stressed patients, growth promotion in livestock,growth retardation associated with the Prader-Willi syndrome andTurner's syndrome, growth retardation in connection with Crohn'sdisease, growth retardation, hair/nail growth maintenance, hipfractures, hunger, hypercortisolism, hyperinsulinemia includingnesidioblastosis, hypothermia, immune deficiency in individuals with adepressed T4/T8 cell ratio, immune response improvement to vaccination,immune system stimulation in companion animals, immune systemstimulation, immunosuppression in immunosuppressed patients,inflammation or inflammatory effects, inflammatory bowel disease,insulin resistance in the heart, insulin resistance in type 2 diabeticpatients, insulin resistance including NIDDM, diabetes, diabetes type I,diabetes type II, intrauterine growth retardation, irritable bowelsyndrome, lipodystrophy, metabolic homeostasis maintenance, milkproduction increase in livestock, muscle mass/strength increase, musclemobility improvement, muscle strength improvement, musclestrength/function maintenance in elderly humans, muscular atrophy,musculoskeletal impairment (e.g. in elderly), Noonan's syndrome, obesityand growth retardation associated with obesity, osteoblast stimulation,osteochondrodysplasias, osteoporosis, ovulation induction (adjuvanttreatment), physiological short stature including growth hormonedeficient children, postoperative ileus, protein catabolic responseattenuation after major surgery/trauma, protein kinase B activityenhancement, psychosocial deprivation, pulmonary dysfunction andventilator dependency, pulmonary function improvement, pulsatile growthhormone release induction, recovery of burn patients and reducinghospitalization of burn patients (acceleration), renal failure orinsufficiency resulting from growth retardation, renal homeostasismaintenance in the frail elderly, sarcopenia, schizophrenia, sensoryfunction maintenance, short bowel syndrome, short stature associatedwith chronic illness, skeletal dysplasia, skin thickness maintenance,sleep disorders, sleep quality improvement, thrombocytopenia, thymicdevelopment stimulation, tooth repair or growth, tumor cellproliferation, ventricular dysfunction or reperfusion events, wasting inconnection with AIDS, wasting in connection with chronic liver disease,wasting in connection with chronic obstructive pulmonary disease (COPD),wasting in connection with multiple sclerosis or other neurodegenerativedisorders, wasting secondary to fractures, wool growth stimulation insheep, wound healing (acceleration) and/or wound healing delay, such asby self diagnosis or medical diagnosis, or are at recognized andappreciated risk of developing such conditions and who use the inventionmethods and compositions to combat these effects. Naturally, one usingthe invention as disclosed will use an amount of the invention compoundsand compositions effective to obtain the desired results. Such amount isinclusive of the amounts described herein.

1. A method for the treatment or prophylaxis of at least onephysiological and/or pathophysiological condition in a mammal that ismediated by GHS receptors, comprising administering to a mammal in needof treatment or prophylaxis of at least one physiological and/orpathophysiological condition that is mediated by GHS receptors aneffective amount of at least one compound according to formula (I)

wherein: R1 and R2 are independently of one another selected from thegroup consisting of hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl,heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl,arylalkylsulfonyl which are optionally substituted in the alkyl,cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,heteroarylalkyl, heterocyclyl and/or heterocyclylalkyl group by up to 3substituents independently selected from the group consisting ofhalogen, —F, —C, —Br, —I, —N₃, —CN, —NR7R8, —OH, —NO₂, alkyl, aryl,arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl; one of radicals R3 and R4 isa hydrogen atom, whereas the other radical is selected from the groupconsisting of hydrogen atom, alkyl, aryl, heteroaryl, arylalkyl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -alkyl-O-aryl,-alkyl-O-arylalkyl, -alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl,-alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl,-alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl,-alkyl-CO-heterocyclyl, -alkyl-CO-heterocyclylalkyl, -alkyl-C(O)O-aryl,-alkyl-C(O)O-arylalkyl, -alkyl-C(O)O-heteroaryl,-alkyl-C(O)O-heteroarylalkyl, -alkyl-C(O)O-heterocyclyl,-alkyl-C(O)O-heterocyclylalkyl, -alkyl-CO—NH₂, -alkyl-CO—OH, -alkyl-NH₂,-alkyl-NH—C(NH)—NH₂, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl,alkyl-5-alkyl, alkyl-S—H which are optionally substituted in the aryl,heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/orheterocyclylalkyl group by up to 3 substituents independently selectedfrom the group consisting of halogen, —F, —Cl, —Br, —I, —N₃, —CN,—NR7R8, —OH, —NO₂, alkyl, aryl, arylalkyl, —O-alkyl, —O-aryl,—O-arylalkyl; R5 is selected from the group consisting of hydrogen atom,alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, —CO-alkyl,—CO-cycloalkyl, —CO-cycloalkylalkyl, —CO-aryl, —CO-arylalkyl,—CO-heteroaryl, —CO-heteroarylalkyl, —CO-heterocyclyl,—CO-heterocyclylalkyl, —CO—C*(R9R10)-NH₂, —CO—CH₂—C—(R9R10)-NH₂,—CQ-C*(R9R10)-CH₂—NH₂, alkylsulfonyl, arylsulfonyl, arylalkylsulfonylwhich are optionally substituted by up to 3 substituents independentlyselected from the group consisting of halogen, —F, —Cl, —Br, —I, —N₃,—CN, —NR7R8, —OH, —NO₂, alkyl, aryl, arylalkyl, —O-alkyl, —O-aryl,—O-arylalkyl; R6 is selected from the group consisting of hydrogen atom,alkyl, cycloalkyl, and cycloalkylalkyl; R7 and R8 are independently ofone another selected from the group consisting of hydrogen atom, alkyl,cycloalkyl, and cycloalkylalkyl; R9 and R10 are independently of oneanother selected from the group consisting of hydrogen atom, alkyl,natural alpha-amino acid side chain, and unnatural alpha-amino acid sidechain; m is 0, 1 or 2; and * means a carbon atom of R or S configurationwhen chiral.
 2. The method as claimed in claim 1, where R3 is selectedfrom the group consisting of -alkyl-CO-aryl, -alkyl-CO-arylalkyl,-alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl,alkyl-CO-heterocyclylalkyl, -alkyl-C(O)O-aryl, -alkyl-C(O)O-arylalkyl,-alkyl-C(O)O-heteroaryl, -alkyl-C(O)O-heteroarylalkyl,-alkyl-C(O)O-heterocyclyl, -alkyl-C(O)O-heterocyclylalkyl,-alkyl-CO—NH₂, -alkyl-CO—OH, -alkyl-NH—C(NH)—NH₂, alkyl-5-alkyl, andalkyl-S—H.
 3. The method as claimed in claims 1, where R4 is a hydrogenatom; R5 is selected from the group consisting of hydrogen atom, alkyl,cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl,arylsulfonyl, arylalkylsulfonyl, —CO-cycloalkyl, —CO-cycloalkyl-alkyl,—CO-aryl, —CO-arylalkyl, —CO-heteroaryl, —CO-heteroarylalkyl,—CO-heterocyclyl, —CO-heterocyclylalkyl; with the proviso that if R5 is—CO-heteroarylalkyl, heteroaryl is not imidazole; and with the provisothat if R5 is —CO-heterocyclyl and heterocyclyl contains only nitrogenatoms as heteroatoms, that at least two nitrogen atoms are contained inheterocyclyl; and with the proviso that if R5 is —CO-heterocyclylalkyland heterocyclyl contains only nitrogen atoms as heteroatoms that in thecase that one or two nitrogen atoms are contained in heterocyclyl nonitrogen atom is positioned at position 1 of heterocyclyl that is theatom directly linking heterocyclyl to the carbonyl group —CO—; wherealkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl,arylsulfonyl, arylalkylsulfonyl, —CO-cycloalkyl, —CO-cycloalkylalkyl,—CO-aryl, —CO-arylalkyl, —CO-heteroaryl, —CO-heteroarylalkyl,—CO-heterocyclyl, and/or —CO-heterocyclylalkyl are optionallysubstituted by up to 3 substituents independently selected from thegroup consisting of halogen, —F, —Cl, —Br, —I, —N₃, —CN, —NR7R8, —OH,—NO₂, alkyl, aryl, arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl; with theproviso that if R5 is —CO-cycloalkyl or —CO-cycloalkylalkyl, R5 is notsubstituted with NR7R8 at position 1 of cycloalkyl, that is the C atomdirectly linking cycloalkyl to the carbonyl group —CO— in case ofR5=—CO-cycloalkyl or to the alkyl in case R5=—CO-cycloalkylalkyl; andwith the proviso that if R5 is —CO-aryl or —CO-arylalkyl and aryl isphenyl/benzene and is only substituted with one substituent, this onesubstituent is not —NR7R8; R6 is a hydrogen atom; R7 and R8 areindependently of one another selected from the group consisting ofhydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl; and m is 0, 1 or 2.4. The method as claimed in claim 1, where R1 is selected from the groupconsisting of hydrogen, methyl, (2-methoxyphenyl)-methyl,(3-methoxyphenyl)-methyl, (4-methoxyphenyl)-methyl,(3-methoxyphenyl)-ethyl, (4-methoxyphenyl)-ethyl, phenyl, phenyl-methyl,phenyl-ethyl, (4-ethylphenyl)-methyl, (4-methylphenyl)-methyl,(4-fluorophenyl)-methyl, (4-bromophenyl)-methyl,(2,4-dimethoxyphenyl)-methyl, (3,5-dimethoxyphenyl)-methyl,2,2-diphenyl-ethyl, naphthaline-1-yl-methyl, 1H-indole-3-yl-methyl,2-(1H-indole-3-yl)-ethyl, 3-(1H-indole-3-yl)-propyl, 4-methyl-phenyl,4-ethyl-phenyl, n-hexyl, (3,4-dichlorophenyl)-methyl,(4-nitro-phenyl)-methyl, (pyridine-2-yl)-methyl, (pyridine-3-yl)-methyl,(pyridine-4-yl)-methyl, (thiophene-2-yl)-methyl,(thiophene-3-yl)-methyl, (furan-2-yl)-methyl, (furan-3-yl)-methyl; R2 isselected from the group consisting of methyl, 1H-indole-3-yl-methyl,2-(1H-indole-3-yl)-ethyl, 3-(1H-indole-3-yl)-propyl, 2-phenyl-ethyl,3-phenyl-propyl, 4-phenyl-butyl, 2-methoxy-phenylmethyl,3-methoxy-phenylmethyl, 4-methoxy-phenylmethyl, 2-methoxy-phenylethyl,3-methoxy-phenylethyl, 4-methoxy-phenylethyl; R3 is selected from thegroup consisting of hydrogen atom, methyl, propan-2-yl,2-methyl-propan-1-yl, butan-2-yl, butan-1-yl, —CH₂—SH, —(CH₂)₂—S—CH₃,1H-indole-3-yl-methyl, phenyl-methyl, 2-phenyl-ethyl, —CH₂—OCH₂-phenyl,—CH₂—CO—CH₂-phenyl, —(CH₂)₂—CO—CH₂-phenyl, —CH₂—C(O)O-phenyl,—(CH₂)₂—C(O)O-phenyl, hydroxy-methyl, 1-hydroxy-ethan-1-yl, —CH₂—CO—NH₂,—(CH₂)₂—CO—NH₂, (1-hydroxy-benzene-4-yl)-methyl, —CH₂—CO—OH,—(CH₂)₂—CO—OH, —(CH₂)₄—NH₂, (1H-imidazol-5-yl)-methyl,—(CH₂)₃—NH—C(NH)—NH₂, —(CH₂)₃—NH₂, and —(CH₂)₃—NH—CO—NH₂; R4 is ahydrogen atom; R5 is selected from the group consisting of hydrogenatom, —CO—CH₂—NH₂ (Gly residue), —CO—CH₂—CH₂—NH₂ (beta-Ala residue),—CO—CHCH₃—NH₂ (D- and/or L-alpha-Ala residue), —CO-(pyrrolidine-2-yl)(D- and/or L-Pro residue), 2-amino-2-carbonyl-propane(2-amino-isobutyric acid/Aib residue), 4-carbonyl-1H-piperidine,3-carbonyl-1H-piperidine, R-(3-carbonyl-1H-piperidine),S-(3-carbonyl-1H-piperidine), 2-carbonyl-1H-piperidine,R-(2-carbonyl-1H-piperidine), S-(2-carbonyl-1H-piperidine),1-amino-2-carbonyl-benzene, carbonyl-cyclohexane, 2-acetyl-pyridine,3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine,3-propionyl-pyridine, 4-propionyl-pyridine,(R-1-amino)-2-carbonyl-cyclohexane, (S-1-amino)-2-carbonyl-cyclohexane,2-carbonyl-1H-imidazole, 2-carbonyl-pyridine, 3-carbonyl-pyridine,4-carbonyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-pyrazine,2-carbonyl-4-hydroxy-1H-pyrrolidine, 4-carbonyl-1H,3H-diazacyclohexane,methyl-sulfonyl, phenylsulfonyl, 1-carbonyl-1-amino-2-phenylethane,phenylmethyl, 1-carbonyl-4-azide-benzene,2-carbonyl-2,5-dihydro-1H-pyrrole, 2-carbonyl-piperazine,2-carbonyl-1H-pyrrolidine, 2-aminoethane, carbonyl-benzene,2-carbonyl-pyrazine, 3-carbonyl-pyrazine, 4-carbonyl-oxacyclohexane,4-methyl-phenylsulfonyl, phenylmethyl-sulfonyl; R6 is a hydrogen atom;and m is
 0. 5. The method as claimed in claim 4, where R3 is selectedfrom the group consisting of —CH₂—CO—CH₂₇-phenyl, —(CH₂)₂—CO—CH₂-phenyl,—CH₂—CO—NH₂, —(CH₂)₂—CO—NH₂, —CH₂—CO—OH, —(CH₂)₂—CO—OH,—(CH₂)₃—NH—C(NH)—NH₂, —CH₂—SH, —(CH₂)₂—S—CH₃.
 6. The method as claimedin claim 4, where R5 is selected from the group consisting of hydrogenatom, methylsulfonyl, phenylsulfonyl, carbonyl-cyclohexane,(R-1-amino)-2-carbonyl-cyclohexane, (S-1-amino)-2-carbonyl-cyclohexane,2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine,2-acetyl-pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine,2-propionyl-pyridine, 3-propionyl-pyridine, 4-propionyl-pyridine,2-amino-3-carbonyl-pyridine, 2-carbonyl-1H-imidazole,2-carbonyl-pyrazine, 4-carbonyl-1H,3H-diazacyclohexane.
 7. The method asclaimed in claim 1 where the compound is at least one compound selectedfrom the group consisting of: compound 1(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 2(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 3(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 4(R)—N-(1-(5-benzyl-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 5(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 6(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 7(R)—N-(1-(4-(3-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 8(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 9(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 10(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 11(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 12(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 13(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 14(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 15(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 16(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 17(R)—N-(1-(4,5-bis(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 18(S)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 19(R)—N-(1-(4-(3-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 20(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 21(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,5-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 22(R)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 23(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 24(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-(3-(1H-indol-3-yl)propyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 25(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2-methoxy)benzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 26(R)—N-(1-(4-(2-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 27(R)—N-(2-(1H-indol-3-yl)-1-(4-(naphthalen-1-ylmethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 28(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,4-dichlorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 29(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-fluorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 30(R)—N-(1-(4-(4-fluorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 31(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 32(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 33(R)—N-(1-(4-(4-methylbenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 34(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 36(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 37(R)—N-(1-(4-(4-methylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 38(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide,compound 39(R)—N-(1-(5-benzyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 40(2S,4R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-hydroxypyrrolidine-2-carboxamide,compound 41(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 42(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 43(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 44(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 45(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 46(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 47(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 48(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 49(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 50(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,44-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 51(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 52(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide,compound 53(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)cyclohexanecarboxamide,compound 54(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 55(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 56(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-aminopropanamide,compound 57(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide,compound 58(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-yl)acetamide,compound 59(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-(pyridin-3-yl)propanamide,compound 60(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 61(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 62(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 63(R)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 64(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 65(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,compound 66(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 67(R)—N-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 68(S)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 69(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide, compound 70(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 71(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 72(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 73(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide, compound 74(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,compound 75(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 76(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 77(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,compound 78(R)—N-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 79(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 80(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 81(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 82(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 83(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 84(R)—N-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 85(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 86(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-cis-aminocyclohexanecarboxamide,compound 87(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,24-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 88(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 89(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 90(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 91(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 92(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 93(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide,compound 94(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide,compound 95(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 96(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 97(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 98(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 99(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 100(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 101(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 102(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 103(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 104(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 105(R)—N-(1-(5-benzyl-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 106(R)—N-(1-(5-benzyl-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 107(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 108(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 109(R)—N-(1-(4,5-dibenzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 110(R)—N-(1-(5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 111(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 112(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 113(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 114(R)—N-(1-(4-(4-bromobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 115(R)—N-(1-(4-(2-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 116(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 117(R)—N-(1-(4,5-diphenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 118(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 119(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,compound 120(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide,compound 121(R)—N-(1-(4-(4-fluorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 122(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 124(R)—N-(1-(4-(4-methylbenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 125(S)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 126(S)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 128N—((R)-1-(4-(4-nitrobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 129(S)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 130(R)—N-(1-(4-(4-methoxyphenethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 131(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 132(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide, compound 133(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-3-carboxamide, compound 134(S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 135N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 136N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide,compound 137(2R)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 138N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 139N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopyridine-3-carboxamide,compound 140(2S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide,compound 141N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,compound 142N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide,compound 143(2S)—N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 144N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2-aminoacetamide,compound 145N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 146N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide,compound 147N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 148N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 149N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 150(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 152N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 153N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-trans-aminocyclohexanecarboxamide,compound 154N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-yl)acetamide,compound 155(3S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 156N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide,compound 157N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 158N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 159N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide, compound 160N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide, compound 161N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)pyrazine-2-carboxamide, compound 162N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-aminoacetamide, compound 163N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide, compound 164N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 165N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-acetamide,compound 166N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 167N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 168N—((R)-1-(5-(4-methoxybenzyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 169N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 170N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-acetamide,compound 171(R)-benzyl-3-(2-aminoisobutyramido)-3-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-propanoate,compound 172N—((R)-1-(5-benzyl-4-((pyridin-3-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 173N—((R)-1-(4-benzyl-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 174N—((R)-2-(1H-indol-3-yl)-1-(4-methyl-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide,compound 175N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 176N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)benzamide,compound 177(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-phenylmethanesulfonylamine,compound 178(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine,compound 179N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 180N-1-((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)ethane-1,2-diamine,compound 181N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 182N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 183N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 184N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-tetrahydro-2H-pyran-4-carboxamide,compound 185N—((R)-1-(5-((1H-indol-3-yl)methyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 186(2S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-3-phenylpropanamide,compound 187(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine,compound 188N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-azidobenzamide,compound 189N-benzyl-(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,compound 190(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2,5-dihydro-1H-pyrrole-2-carboxamide.8. The method as claimed in claim 1 where the treatment is achieved bymodulation of GHS receptors.
 9. The method as claimed in claim 1 wherethe compound is a GHS receptor antagonist.
 10. The method as claimed inclaim 7, where the compound is a GHS receptor antagonist selected fromthe group consisting of: compound 1, 3, 12, 13, 14, 18, 20, 22, 23, 33,36, 37, 38, 41, 46, 47, 48, 49, 50, 51, 52, 53, 57, 58, 59, 60, 61, 63,64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 79, 80, 82, 85, 86,87, 88, 89, 90, 91, 93, 101, 102, 109, 114, 116, 119, 134, 135, 136,137, 138, 139, 140, 145, 146, 147, 148, 150, 152, 153, 154, 156, 157,159, 160, 161, 164, 171, 174, 176, 178, 179, 182, 184, 186, 188 and/orcompound
 190. 11. The method as claimed in claim 9 where the compound isa GHS receptor agonist for GHS receptors selected from the groupconsisting of GHS type 1 receptor, GHS-R 1a, GHS-R 1b, motilin receptor,motilin receptor 1a, neurotensin receptor, TRH receptor, GPR38 (FM1),GPR39 (FM2), FM3, GHS-R subtype, GHS binding site, cardiac GHS-R, andmammary GHS-R.
 12. The method as claimed in claim 9, where the GHSreceptor agonist is selected from the group consisting of: compound 2,4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 17, 19, 21, 24, 25, 26, 27, 28, 29,30, 31, 32, 34, 39, 40, 42, 43, 44, 45, 54, 55, 56, 62, 67, 78, 81, 83,84, 87, 92, 94, 99, 103, 104, 105, 106, 107, 108, 110, 111, 115, 117,118, 121, 122, 124, 130, 131, 142, 155, 158, 163, 173, 175, 180, 181,183, 185 and/or compound
 187. 13. The method as claimed in claim 1 wherethe mammal is selected from the group consisting of human, domesticanimals, cattle, livestock, pets, cow, sheep, pig, goat, horse, pony,donkey, hinny, mule, hare, rabbit, cat, dog, guinea pig, hamster, rat,and mouse.
 14. The method as claimed in claim 1 where the compound is aGHS receptor agonist for GHS receptors selected from the groupconsisting of GHS type 1 receptor, GHS-R 1a, GHS-R 1b, motilin receptor,motilin receptor 1a, neurotensin receptor, TRH receptor, GPR38 (FM1),GPR39 (FM2), FM3, GHS-R subtype, GHS binding site, cardiac GHS-R, andmammary GHS-R.
 15. The method as claimed in claim 1 where thephysiological and/or pathophysiological conditions are selected from thegroup consisting of acute fatigue syndrome and muscle loss followingelection surgery, adipogenesis, adiposity, age-related decline of thymicfunction, age-related functional decline (ARFD) in the elderly, agingdisorder in companion animals, Alzheimer's disease, anorexia; anxiety,blood pressure (lowering), body weight gain/reduction, bone fracturerepair (acceleration), bone remodeling stimulation, cachexia and proteinloss reduction due to chronic illness such as cancer or AIDS, cardiacdysfunctions, cardiomyopathy, cartilage growth stimulation, catabolicdisorders in connection with pulmonary dysfunction and ventilatordependency, catabolic side effects of glucocorticoids, catabolic stateof aging, central nervous system disorders (in combination withantidepressants), chronic dialysis, chronic fatigue syndrome (CFS),cognitive function improvement, complicated fractures, complicationsassociated with transplantation, congestive heart failure (alone/incombination with corticotropin releasing factor antagonists), Crohn'sdisease and ulcerative colits, Cushing's syndrome, dementia,depressions, short-, medium- and/or long-term regulation of energybalance, short-, medium- and/or long-term regulation of food intake(stimulation and/or inhibition), fraility, gastrectomy (ghrelinreplacement therapy), gastric postoperative ileus, glycemic controlimprovement, growth hormone release stimulation in the elderly, growthhormone replacement in stressed patients, growth promotion in livestock,growth retardation associated with the Prader-Willi syndrome andTurner's syndrome, growth retardation in connection with Crohn'sdisease, growth retardation, hair/nail growth maintenance, hipfractures, hunger, hypercortisolism, hyperinsulinemia includingnesidioblastosis, hypothermia, immune deficiency in individuals with adepressed T4/T8 cell ratio, immune response improvement to vaccination,immune system stimulation in companion animals, immune systemstimulation, immunosuppression in immunosuppressed patients,inflammation or inflammatory effects, inflammatory bowel disease,insulin resistance in the heart, insulin resistance in type 2 diabeticpatients, insulin resistance including NIDDM, diabetes, diabetes type I,diabetes type II, intrauterine growth retardation, irritable bowelsyndrome, lipodystrophy, metabolic homeostasis maintenance, milkproduction increase in livestock, muscle mass/strength increase, musclemobility improvement, muscle strength improvement, musclestrength/function maintenance in elderly humans, muscular atrophy,musculoskeletal impairment (e.g. in elderly), Noonan's syndrome, obesityand growth retardation associated with obesity, osteoblast stimulation,osteochondrodysplasias, osteoporosis, ovulation induction (adjuvanttreatment), physiological short stature including growth hormonedeficient children, postoperative ileus, protein catabolic responseattenuation after major surgery/trauma, protein kinase B activityenhancement, psychosocial deprivation, pulmonary dysfunction andventilator dependency, pulmonary function improvement, pulsatile growthhormone release induction, recovery of burn patients and reducinghospitalization of burn patients (acceleration), renal failure orinsufficiency resulting from growth retardation, renal homeostasismaintenance in the frail elderly, sarcopenia, schizophrenia, sensoryfunction maintenance, short bowel syndrome, short stature associatedwith chronic illness, skeletal dysplasia, skin thickness maintenance,sleep disorders, sleep quality improvement, thrombocytopenia, thymicdevelopment stimulation, tooth repair or growth, tumor cellproliferation, ventricular dysfunction or reperfusion events, wasting inconnection with AIDS, wasting in connection with chronic liver disease,wasting in connection with chronic obstructive pulmonary disease (COPD),wasting in connection with multiple sclerosis or other neurodegenerativedisorders, wasting secondary to fractures, wool growth stimulation insheep, wound healing (acceleration) and/or wound healing delay.
 16. Themethod as claimed in claim 15 where physiological and/orpathophysiological conditions are selected from the group consisting ofgrowth retardation, cachexia, short-, medium- and/or long termregulation of energy balance; short-, medium- and/or long termregulation (stimulation and/or inhibition) of food intake; adipogenesis,adiposity and/or obesity; body weight gain and/or reduction; diabetes,diabetes type I, diabetes type II, tumor cell proliferation;inflammation, inflammatory effects, gastric postoperative ileus,postoperative ileus and/or gastrectomy (ghrelin replacement therapy) 17.The method as claimed in claim 1 further comprising administering atleast one additional pharmacologically active substance.
 18. The methodas claimed in claim 17, further comprising administering a GHS receptorantagonist and an endocannabinoid receptor antagonist.
 19. The method asclaimed in claim 1 where the administration is before and/or duringand/or after treatment with at least one additional pharmacologicallyactive substance.
 20. The method as claimed in claim 19, comprisingadministering a GHS receptor antagonist and an endocannabinoid receptorantagonist.
 21. A triazole compound selected from the group consistingof: compound 1(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 2(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 3(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 4(R)—N-(1-(5-benzyl-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 5(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 6(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 7(R)—N-(1-(4-(3-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 8(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 9(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 10(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 11(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(naphthalen-1-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 12(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 13(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 14(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 15(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 16(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 17(R)—N-(1-(4,5-bis(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 18(S)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 19(R)—N-(1-(4-(3-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 20(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 21(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,5-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 22(R)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,24-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 23(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 24(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-(3-(1H-indol-3-yl)propyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 25(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2-methoxy)benzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 26(R)—N-(1-(4-(2-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 27(R)—N-(2-(1H-indol-3-yl)-1-(4-(naphthalen-1-ylmethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 28(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(3,4-dichlorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 29(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-fluorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 30(R)—N-(1-(4-(4-fluorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 31(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 32(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 33(R)—N-(1-(4-(4-methylbenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 34(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methylbenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 36(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 37(R)—N-(1-(4-(4-methylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 38(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide,compound 39(R)—N-(1-(5-benzyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 40(2S,4R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-hydroxypyrrolidine-2-carboxamide,compound 41(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 42(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 43(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 44(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 45(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 46(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 47(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 48(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 49(R)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 50(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 51(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 52(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide,compound 53(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)cyclohexanecarboxamide,compound 54(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 55(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 56(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-aminopropanamide,compound 57(S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide,compound 58(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-yl)acetamide,compound 59(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-3-(pyridin-3-yl)propanamide,compound 60(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 61(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 62(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 63(R)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 64(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 65(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,compound 66(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 67(R)—N-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 68(S)—N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 69(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide, compound 70(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 71(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 72(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 73(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide, compound 74(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,compound 75(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 76(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 77(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,compound 78(R)—N-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 79(R)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 80(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 81(R)—N-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 82(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 83(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 84(R)—N-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide,compound 85(R)—N-(1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide,compound 86(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-cis-aminocyclohexanecarboxamide,compound 87(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 88(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 89(S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 90(R)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 91(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 92(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-bromobenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 93(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide,compound 94(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide,compound 95(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 96(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 97(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 98(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 99(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 100(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-methyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 101(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 102(R)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 103(R)—N-(1-(5-(3-(1H-indol-3-yl)propyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 104(R)—N-(1-(5-((1H-indol-3-yl)methyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 105(R)—N-(1-(5-benzyl-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 106(R)—N-(1-(5-benzyl-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 107(R)—N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,2-diphenylethyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 108(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 109(R)—N-(1-(4,5-dibenzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 110(R)—N-(1-(5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 111(R)—N-(1-(4-(2-(1H-indol-3-yl)ethyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 112(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 113(R)—N-(1-(4-(3,5-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 114(R)—N-(1-(4-(4-bromobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 115(R)—N-(1-(4-(2-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 116(S)—N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 117(R)—N-(1-(4,5-diphenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 118(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 119(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,compound 120(R)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-phenylethyl)-2-amino-2-methylpropanamide,compound 121(R)—N-(1-(4-(4-fluorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 122(R)—N-(1-(4-(3,4-dichlorobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 124(R)—N-(1-(4-(4-methylbenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 125(S)—N-(1-(4-(4-methoxybenzyl)-5-(3-phenylpropyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 126(S)—N-(1-(4-(4-methoxybenzyl)-5-benzyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 128N—((R)-1-(4-(4-nitrobenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 129(S)—N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 130(R)—N-(1-(4-(4-methoxyphenethyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 131(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 132(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)-2-amino-2-methylpropanamide, compound 133(R)—N-(2-(1H-indol-3-yl)-1-(5-phenethyl-4-(pyridin-2-ylmethyl)-4H-1,2,4-triazol-3-yl)ethyl)piperidine-3-carboxamide, compound 134(S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 135N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 136N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide,compound 137(2R)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-2-carboxamide,compound 138N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 139N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopyridine-3-carboxamide,compound 140(2S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminopropanamide,compound 141N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)isonicotinamide,compound 142N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide,compound 143(2S)—N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 144N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2-aminoacetamide,compound 145N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 146N—((R)-2-(1H-indol-3-yl)-1-(5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide,compound 147N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 148N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide,compound 149N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 150(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrrolidine-2-carboxamide,compound 152N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide,compound 153N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-trans-aminocyclohexanecarboxamide,compound 154N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-yl)acetamide,compound 155(3S)—N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-3-carboxamide,compound 156N—((R)-1-(4-(4-ethylbenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminobenzamide,compound 157N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 158N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 159N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide, compound 160N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-(pyridin-2-yl)acetamide, compound 161N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)pyrazine-2-carboxamide, compound 162N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)-2-aminoacetamide, compound 163N—((R)-2-(1H-indol-3-yl)-1-(4-(2,4-dimethoxyphenyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)piperidine-4-carboxamide, compound 164N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 165N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-acetamide,compound 166N—((R)-1-(5-benzyl-4-((pyridin-2-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 167N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 168N—((R)-1-(5-(4-methoxybenzyl)-4-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 169N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 170N—((R)-1-(5-benzyl-4-((pyridin-4-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-acetamide,compound 171(R)-benzyl-3-(2-aminoisobutyramido)-3-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-propanoate,compound 172N—((R)-1-(5-benzyl-4-((pyridin-3-yl)methyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 173N—((R)-1-(4-benzyl-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 174N—((R)-2-(1H-indol-3-yl)-1-(4-methyl-5-phenethyl-4H-1,2,4-triazol-3-yl)ethyl)picolinamide,compound 175N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 176N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)benzamide,compound 177(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-phenylmethanesulfonylamine,compound 178(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine,compound 179N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 180N-1-((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)ethane-1,2-diamine,compound 181N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 182N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide,compound 183N—((R)-1-(4-((furan-2-yl)methyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperidine-4-carboxamide,compound 184N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-tetrahydro-2H-pyran-4-carboxamide,compound 185N—((R)-1-(5-((1H-indol-3-yl)methyl)-4-(3-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-2-methylpropanamide,compound 186(2S)—N—((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-amino-3-phenylpropanamide,compound 187(R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)-N-tosylethanamine,compound 188N—((R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-4-azidobenzamide,compound 189N-benzyl-(R)-1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine,compound 190(2S)—N—((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2,5-dihydro-1H-pyrrole-2-carboxamide.22. A pharmaceutical composition comprising at least one compound asclaimed in claim 21 and pharmaceutically acceptable carrier and/orexcipient.
 23. The pharmaceutical composition as claimed in claim 22,where the active ingredient is present in a unit dose of from 0.001 mgto 100 mg per kg of a patient's bodyweight.
 24. The pharmaceuticalcomposition as claimed in claim 22, where the composition comprises atleast one further pharmacologically active substance.
 25. Thepharmaceutical composition as claimed in claim 24, where the furtherpharmacologically active substance is an endocannabinoid receptorantagonist.